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Wang C, Zhang T, Guan Y, Han B, Wu S, Wang X, Yu J, Zhang J, Zhang G, Miao Q, Su S. Fatty acid binding protein 4 regulates doxorubicin-induced renal injury via mediating lipid metabolism and apoptosis. Chem Biol Interact 2025; 408:111419. [PMID: 39922518 DOI: 10.1016/j.cbi.2025.111419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 12/24/2024] [Accepted: 02/06/2025] [Indexed: 02/10/2025]
Abstract
Doxorubicin(DOX) is an anthracycline chemotherapeutic drug used in the treatment of a wide range of tumors. However, the nephrotoxicity has limited the clinical application of DOX. Fatty acid-binding protein 4 (FABP4), a key adipokine mainly expressed in adipocytes, is strongly associated with kidney dysfunction and kidney disease. This study aims to investigate the role of FABP4 in DOX-induced nephrotoxicity. In vivo experiments, the mice were divided into 4 groups randomly: CON group, DOX group, 4T1 group, and 4T1 + DOX group respectively. DOX was given by intraperitoneal injection at a dose of 15 mg/kg. The kidney function indicators, the morphology and lipid deposition in renal tissues and the preliminary mechanism were assessed. In vitro experiment, HK-2 cell was used to detect DOX-induced kidney cell injury with or without BMS309403. DOX caused renal dysfunction in both DOX group and 4T1 + DOX group, with a more severe kidney injury in DOX group. DOX also induced kidney lipid deposition, glycerophospholipids metabolism dysfunction, apoptosis accompanied by increased FABP4 and decreased Peroxisome Proliferator Activated Receptor- γ (PPAR-γ) levels in the kidney tissues. The decreased cell viability, increased apoptotic ratio, elevated protein levels of apoptosis and the lipid deposition caused by DOX were all alleviated by BMS309403. FABP4 mediated DOX induced kidney damage in normal mice and tumor-bearing mice by lipid metabolism disorders and cell apoptosis. This study may enhance the clinical management of DOX-induced kidney injury and provide new therapeutic targets and preventive strategies for the clinical application of DOX.
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Affiliation(s)
- Chuchu Wang
- Department of Pharmacology, The Key Laboratory of Pharmacology and Toxicology for New Drugs, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, PR China
| | - Tao Zhang
- Department of Pharmacology, The Key Laboratory of Pharmacology and Toxicology for New Drugs, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, PR China; Department of Intensive Care Unit (ICU), The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
| | - Yufeng Guan
- Department of Pharmacology, The Key Laboratory of Pharmacology and Toxicology for New Drugs, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, PR China
| | - Boye Han
- Department of Pharmacology, The Key Laboratory of Pharmacology and Toxicology for New Drugs, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, PR China
| | - Shang Wu
- Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
| | - Xu Wang
- School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China
| | - Jing Yu
- Department of Pharmacy, First Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Junxia Zhang
- Department of Nephrology, Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, PR China
| | - Guoqiang Zhang
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
| | - Qingfeng Miao
- Department of Pharmacology, The Key Laboratory of Pharmacology and Toxicology for New Drugs, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, PR China
| | - Suwen Su
- Department of Pharmacology, The Key Laboratory of Pharmacology and Toxicology for New Drugs, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, PR China.
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Wu J, Tang G, Cheng CS, Yeerken R, Chan YT, Fu Z, Zheng YC, Feng Y, Wang N. Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery. Mol Cancer 2024; 23:218. [PMID: 39354529 PMCID: PMC11443773 DOI: 10.1186/s12943-024-02136-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 09/20/2024] [Indexed: 10/03/2024] Open
Abstract
Hepatic, biliary, and pancreatic cancer pose significant challenges in the field of digestive system diseases due to their highly malignant nature. Traditional Chinese medicine (TCM) has gained attention as a potential therapeutic approach with long-standing use in China and well-recognized clinical benefits. In this review, we systematically summarized the clinical applications of TCM that have shown promising results in clinical trials in treating hepatic, biliary, and pancreatic cancer. We highlighted several commonly used TCM therapeutics with validated efficacy through rigorous clinical trials, including Huaier Granule, Huachansu, and Icaritin. The active compounds and their potential targets have been thoroughly elucidated to offer valuable insights into the potential of TCM for anti-cancer drug discovery. We emphasized the importance of further research to bridge the gap between TCM and modern oncology, facilitating the development of evidence-based TCM treatment for these challenging malignancies.
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Affiliation(s)
- Junyu Wu
- School of Chinese Medicine, the University of Hong Kong, 3, Sasson Road, Pokfulam, Hong Kong
| | - Guoyi Tang
- School of Chinese Medicine, the University of Hong Kong, 3, Sasson Road, Pokfulam, Hong Kong
| | - Chien-Shan Cheng
- Department of Digestive Endoscopy Center & Gastroenterology, Shuguang Hospital Affiliated With Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China
| | - Ranna Yeerken
- School of Chinese Medicine, the University of Hong Kong, 3, Sasson Road, Pokfulam, Hong Kong
| | - Yau-Tuen Chan
- School of Chinese Medicine, the University of Hong Kong, 3, Sasson Road, Pokfulam, Hong Kong
| | - Zhiwen Fu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi-Chao Zheng
- State Key Laboratory of Esophageal Cancer Prevention &, Treatment Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China
| | - Yibin Feng
- School of Chinese Medicine, the University of Hong Kong, 3, Sasson Road, Pokfulam, Hong Kong.
| | - Ning Wang
- School of Chinese Medicine, the University of Hong Kong, 3, Sasson Road, Pokfulam, Hong Kong.
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3
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Jiang Y, Zeng Z, He G, Liu M, Liu C, Liu M, Lv T, Wang A, Wang Y, Zhao M, Wang K, Zhang M. Genome-wide identification and integrated analysis of the FAR1/FHY3 gene family and genes expression analysis under methyl jasmonate treatment in Panax ginseng C. A. Mey. BMC PLANT BIOLOGY 2024; 24:549. [PMID: 38872078 DOI: 10.1186/s12870-024-05239-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Accepted: 06/03/2024] [Indexed: 06/15/2024]
Abstract
Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.
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Affiliation(s)
- Yang Jiang
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Zixia Zeng
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Gaohui He
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Mengna Liu
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Chang Liu
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Mingming Liu
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Tingting Lv
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Aimin Wang
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Yi Wang
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Mingzhu Zhao
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China.
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China.
| | - Kangyu Wang
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China.
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China.
| | - Meiping Zhang
- College of Life Science, Jilin Agricultural University, Changchun, Jilin, 130118, China.
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Jilin Agricultural University, Changchun, Jilin, 130118, China.
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Zhang S, Zheng B, Wei Y, Liu Y, Yang L, Qiu Y, Su J, Qiu M. Bioinspired ginsenoside Rg3 PLGA nanoparticles coated with tumor-derived microvesicles to improve chemotherapy efficacy and alleviate toxicity. Biomater Sci 2024; 12:2672-2688. [PMID: 38596867 DOI: 10.1039/d4bm00159a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Breast cancer, a pervasive malignancy affecting women, demands a diverse treatment approach including chemotherapy, radiotherapy, and surgical interventions. However, the effectiveness of doxorubicin (DOX), a cornerstone in breast cancer therapy, is limited when used as a monotherapy, and concerns about cardiotoxicity persist. Ginsenoside Rg3, a classic compound of traditional Chinese medicine found in Panax ginseng C. A. Mey., possesses diverse pharmacological properties, including cardiovascular protection, immune modulation, and anticancer effects. Ginsenoside Rg3 is considered a promising candidate for enhancing cancer treatment when combined with chemotherapy agents. Nevertheless, the intrinsic challenges of Rg3, such as its poor water solubility and low oral bioavailability, necessitate innovative solutions. Herein, we developed Rg3-PLGA@TMVs by encapsulating Rg3 within PLGA nanoparticles (Rg3-PLGA) and coating them with membranes derived from tumor cell-derived microvesicles (TMVs). Rg3-PLGA@TMVs displayed an array of favorable advantages, including controlled release, prolonged storage stability, high drug loading efficiency and a remarkable ability to activate dendritic cells in vitro. This activation is evident through the augmentation of CD86+CD80+ dendritic cells, along with a reduction in phagocytic activity and acid phosphatase levels. When combined with DOX, the synergistic effect of Rg3-PLGA@TMVs significantly inhibits 4T1 tumor growth and fosters the development of antitumor immunity in tumor-bearing mice. Most notably, this delivery system effectively mitigates the toxic side effects of DOX, particularly those affecting the heart. Overall, Rg3-PLGA@TMVs provide a novel strategy to enhance the efficacy of DOX while simultaneously mitigating its associated toxicities and demonstrate promising potential for the combined chemo-immunotherapy of breast cancer.
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Affiliation(s)
- Shulei Zhang
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Bo Zheng
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Yiqi Wei
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Yuhao Liu
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lan Yang
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Yujiao Qiu
- The Wharton School and School of Nursing, University of Pennsylvania, 19104, Philadelphia, USA
| | - Jing Su
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Mingfeng Qiu
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
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5
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Lee JS, Lee HY. Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells. J Ginseng Res 2024; 48:266-275. [PMID: 38707642 PMCID: PMC11068999 DOI: 10.1016/j.jgr.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 01/31/2024] [Accepted: 03/07/2024] [Indexed: 05/07/2024] Open
Abstract
Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.
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Affiliation(s)
- Ji-Sun Lee
- Department of Molecular, Cell & Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Ho-Young Lee
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
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6
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Feng F, Ko HA, Truong TMT, Song WJ, Ko EJ, Kang I. Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation. Sci Rep 2024; 14:9157. [PMID: 38644456 PMCID: PMC11033271 DOI: 10.1038/s41598-024-59758-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 04/15/2024] [Indexed: 04/23/2024] Open
Abstract
Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 μM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.
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Affiliation(s)
- Fang Feng
- Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, Korea
| | - Hyun-A Ko
- Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, Korea
| | - Thi My Tien Truong
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Korea
| | - Woo-Jin Song
- College of Veterinary Medicine, Jeju National University, Jeju, 63243, Korea
| | - Eun-Ju Ko
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Korea
- College of Veterinary Medicine, Jeju National University, Jeju, 63243, Korea
| | - Inhae Kang
- Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, Korea.
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Korea.
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7
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Ning JY, Zhang ZH, Zhang J, Liu YM, Li GC, Wang AM, Li Y, Shan X, Wang JH, Zhang X, Zhao Y. Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability. Am J Cancer Res 2024; 14:601-615. [PMID: 38455405 PMCID: PMC10915333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 01/28/2024] [Indexed: 03/09/2024] Open
Abstract
Breast cancer stem cells (BCSCs) are responsible for breast cancer metastasis, recurrence and treatment resistance, all of which make BCSCs potential drivers of breast cancer aggression. Ginsenoside Rg3, a traditional Chinese herbal medicine, was reported to have multiple antitumor functions. Here, we revealed a novel effect of Rg3 on BCSCs. Rg3 inhibits breast cancer cell viability in a dose- and time-dependent manner. Importantly, Rg3 suppressed mammosphere formation, reduced the expression of stemness-related transcription factors, including c-Myc, Oct4, Sox2 and Lin28, and diminished ALDH(+) populations. Moreover, tumor-bearing mice treated with Rg3 exhibited robust delay of tumor growth and a decrease in tumor-initiating frequency. In addition, we found that Rg3 suppressed breast cancer stem-like properties mainly through inhibiting MYC expression. Mechanistically, Rg3 accelerated the degradation of MYC mRNA by enhancing the expression of the let-7 family, which was demonstrated to bind to the MYC 3' untranslated region (UTR). In conclusion, our findings reveal the remarkable suppressive effect of Rg3 on BCSCs, suggesting that Rg3 is a promising therapeutic treatment for breast cancer.
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Affiliation(s)
- Jin-Yue Ning
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDalian 116011, Liaoning, China
| | - Zi-Han Zhang
- Medical College of Tianjin UniversityTianjin 300072, China
| | - Jia Zhang
- Department of Oncology, People’s Hospital of NingxiangNingxiang 410600, Hunan, China
| | - Yong-Min Liu
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDalian 116011, Liaoning, China
| | - Guan-Chu Li
- National Clinical Research Center for Gynecology and Obstetrics, Tongji Medical College, Tongji Hospital, Huazhong University of Science and TechnologyWuhan 430000, China
| | - A-Man Wang
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDalian 116011, Liaoning, China
| | - Ying Li
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDalian 116011, Liaoning, China
| | - Xiu Shan
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDalian 116011, Liaoning, China
| | - Ju-Hong Wang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021, China
| | - Xu Zhang
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University Cardiovascular HospitalDalian 116000, Liaoning, China
| | - Yi Zhao
- Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDalian 116011, Liaoning, China
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Liu C, Zhao M, Ma H, Zhang Y, Liu Q, Liu S, Wang Y, Wang K, Zhang M, Wang Y. The NAC Transcription Factor PgNAC41-2 Gene Involved in the Regulation of Ginsenoside Biosynthesis in Panax ginseng. Int J Mol Sci 2023; 24:11946. [PMID: 37569353 PMCID: PMC10418625 DOI: 10.3390/ijms241511946] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 07/21/2023] [Accepted: 07/23/2023] [Indexed: 08/13/2023] Open
Abstract
Ginseng (Panax ginseng C.A. Meyer) is a perennial herb of the Araliaceae family, a traditional and valuable Chinese herb in China. The main active component of ginseng is ginsenoside. The NAC transcription factors belong to a large family of plant-specific transcription factors, which are involved in growth and development, stress response and secondary metabolism. In this study, we mapped the NAC gene family on 24 pairs of ginseng chromosomes and found numerous gene replications in the genome. The NAC gene PgNAC41-2, found to be highly related to ginsenoside synthesis, was specifically screened. The phylogeny and expression pattern of the PgNAC41-2 gene were analyzed, along with the derived protein sequence, and a structure model was generated. Furthermore, the PgNAC41-2 gene was cloned and overexpressed by a Rhizobium rhizogenes mediated method, using ginseng petioles as receptor material. The saponin content of the transformed material was analyzed to verify the function of the NAC transcription factor in ginseng. Our results indicate that the PgNAC41-2 gene positively regulates the biosynthesis of saponins.
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Affiliation(s)
- Chang Liu
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Changchun 130118, China
| | - Mingzhu Zhao
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Changchun 130118, China
| | - Hedan Ma
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
| | - Yu Zhang
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
| | - Qian Liu
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
| | - Sizhang Liu
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Changchun 130118, China
| | - Yanfang Wang
- Laboratory for Cultivation and Breeding of Medicinal Plants of National Administration of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China;
| | - Kangyu Wang
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Changchun 130118, China
| | - Meiping Zhang
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Changchun 130118, China
| | - Yi Wang
- College of Life Science, Jilin Agricultural University, Changchun 130118, China; (C.L.); (H.M.); (Y.Z.); (Q.L.); (S.L.); (K.W.); (M.Z.)
- Jilin Engineering Research Center Ginseng Genetic Resources Development and Utilization, Changchun 130118, China
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9
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Huang Q, Pan X, Zhu W, Zhao W, Xu H, Hu K. Natural Products for the Immunotherapy of Glioma. Nutrients 2023; 15:2795. [PMID: 37375698 DOI: 10.3390/nu15122795] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/15/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Glioma immunotherapy has attracted increasing attention since the immune system plays a vital role in suppressing tumor growth. Immunotherapy strategies are already being tested in clinical trials, such as immune checkpoint inhibitors (ICIs), vaccines, chimeric antigen receptor T-cell (CAR-T cell) therapy, and virus therapy. However, the clinical application of these immunotherapies is limited due to their tremendous side effects and slight efficacy caused by glioma heterogeneity, antigen escape, and the presence of glioma immunosuppressive microenvironment (GIME). Natural products have emerged as a promising and safe strategy for glioma therapy since most of them possess excellent antitumor effects and immunoregulatory properties by reversing GIME. This review summarizes the status of current immunotherapy strategies for glioma, including their obstacles. Then we discuss the recent advancement of natural products for glioma immunotherapy. Additionally, perspectives on the challenges and opportunities of natural compounds for modulating the glioma microenvironment are also illustrated.
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Affiliation(s)
- Qi Huang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xier Pan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wenhao Zhu
- Department of Anaesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Wen Zhao
- Department of Anaesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Hongzhi Xu
- Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
- National Center for Neurological Disorders, Shanghai 200040, China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai 200040, China
- Neurosurgical Institute, Fudan University, Shanghai 200040, China
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China
| | - Kaili Hu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Kim JH, Shin JS, Kim W, Lee H, Baik MY. Effects of Puffing, Acid, and High Hydrostatic Pressure Treatments on Ginsenoside Profile and Antioxidant Capacity of Mountain-Cultivated Panax ginseng. Foods 2023; 12:foods12112174. [PMID: 37297419 DOI: 10.3390/foods12112174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/18/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
The purpose of this study was to investigate the effects of puffing, acid, and high hydrostatic pressure (HHP) treatments on the ginsenoside profile and antioxidant capacity of mountain-cultivated Panax ginseng (MCPG) before and after treatments. Puffing and HHP treatments decreased extraction yield and increased crude saponin content. The combination of puffing and HHP treatment showed significantly higher crude saponin content than each single treatment. Puffing treatment showed the highest ginsenoside conversion compared with HHP and acid treatments. Significant ginsenoside conversion was not observed in HHP treatment but was in acid treatment. When the puffing and acid treatments were combined, Rg3 and compound K content (1.31 mg and 10.25 mg) was significantly higher than that of the control (0.13 mg and 0.16 mg) and acid treatment (0.27 mg and 0.76 mg). No synergistic effect was observed between acid and HHP treatments. In the case of functional properties, the puffing treatment showed a significant increase in TFC (29.6%), TPC (1072%), and DPPH radical scavenging capacity (2132.9%) compared to the control, while acid and HHP combined treatments did not significantly increase; therefore, the synergistic effects of HHP/puffing and acid/puffing treatments were observed in crude saponin content and ginsenoside conversion, respectively. Consequently, puffing combined with acid or HHP treatments may provide new ways to produce high-value-added MCPG with a higher content of Rg3 and compound K or crude saponin compared to untreated MCPG.
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Affiliation(s)
- Jang-Hwan Kim
- Department of Food Science and Biotechnology, Institute of Life Science and Resources, Kyung Hee University, Yongin 17104, Republic of Korea
| | - Jae-Sung Shin
- Department of Food Science and Biotechnology, Institute of Life Science and Resources, Kyung Hee University, Yongin 17104, Republic of Korea
| | - Wooki Kim
- Department of Food Science and Biotechnology, Institute of Life Science and Resources, Kyung Hee University, Yongin 17104, Republic of Korea
| | - Hyungjae Lee
- Department of Food Engineering, Dankook University, Cheonan 31116, Republic of Korea
| | - Moo-Yeol Baik
- Department of Food Science and Biotechnology, Institute of Life Science and Resources, Kyung Hee University, Yongin 17104, Republic of Korea
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Xiong J, Yuan H, Fei S, Yang S, You M, Liu L. The preventive role of the red gingeng ginsenoside Rg3 in the treatment of lung tumorigenesis induced by benzo(a)pyrene. Sci Rep 2023; 13:4528. [PMID: 36941308 PMCID: PMC10027881 DOI: 10.1038/s41598-023-31710-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 03/16/2023] [Indexed: 03/23/2023] Open
Abstract
Red ginseng has been used in traditional medicine for centuries in Asia. In this study, we evaluated four types of red ginseng grown in different areas (Chinese red ginseng, Korean red ginseng A, Korean red ginseng B, and Korean red ginseng C) for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene (B(a)P) in A/J mice and found that Korean red ginseng B was the most effective at lowering the tumor load among the four red ginseng varieties. Moreover, we analyzed the levels of various ginsenosides (Rg1, Re, Rc, Rb2, Rb3, Rb1, Rh1, Rd, Rg3, Rh2, F1, Rk1, and Rg5) in four kinds of red ginseng extract and found that Korean red ginseng B had the highest level of ginsenoside Rg3 (G-Rg3), which suggested that G-Rg3 may play an important role in its therapeutic efficacy. This work revealed that the bioavailability of G-Rg3 was relatively poor. However, when G-Rg3 was coadministered with verapamil, a P-glycoprotein inhibitor, the G-Rg3 efflux in Caco-2 cells was lowered, the small intestinal absorption rate of G-Rg3 in the rat models was increased, the concentration levels of G-Rg3 were elevated in the intestine and plasma, and its tumor-preventive abilities in the tumorigenesis rat model induced by B(a)P were also augmented. We also found that G-Rg3 reduced B(a)P-induced cytotoxicity and DNA adduct formation in human lung cells and rescued phase II enzyme expression and activity through Nrf2 pathways, which may be the potential mechanisms underlying the inhibitory effects of G-Rg3 on lung tumorigenesis. Our study showed a potentially vital role of G-Rg3 in targeting lung tumors in murine models. The oral bioavailability of this ginsenoside was augmented by targeting P-glycoprotein, which allowed the molecule to exert its anticancer effects.
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Affiliation(s)
- Jie Xiong
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hongmei Yuan
- Department of Pathology, Wuhan Jinyintan Hospital, Wuhan, 430023, China
| | - Shihong Fei
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shengli Yang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ming You
- Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX, 77030, USA.
| | - Li Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Majnooni MB, Fakhri S, Ghanadian SM, Bahrami G, Mansouri K, Iranpanah A, Farzaei MH, Mojarrab M. Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways. Metabolites 2023; 13:metabo13030323. [PMID: 36984763 PMCID: PMC10052344 DOI: 10.3390/metabo13030323] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/06/2023] [Accepted: 02/16/2023] [Indexed: 02/25/2023] Open
Abstract
Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.
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Affiliation(s)
- Mohammad Bagher Majnooni
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Syed Mustafa Ghanadian
- Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran
| | - Gholamreza Bahrami
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Kamran Mansouri
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran
| | - Amin Iranpanah
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
- Correspondence: or (M.H.F.); (M.M.); Tel.: +98-08334266780 (M.M.)
| | - Mahdi Mojarrab
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
- Correspondence: or (M.H.F.); (M.M.); Tel.: +98-08334266780 (M.M.)
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Recent advances in ginsenosides against respiratory diseases: Therapeutic targets and potential mechanisms. Biomed Pharmacother 2023; 158:114096. [PMID: 36502752 DOI: 10.1016/j.biopha.2022.114096] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/30/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Respiratory diseases mainly include asthma, influenza, pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, lung fibrosis, and lung cancer. Given their high prevalence and poor prognosis, the prevention and treatment of respiratory diseases are increasingly essential. In particular, the development for the novel strategies of drug treatment has been a hot topic in the research field. Ginsenosides are the major component of Panax ginseng C. A. Meyer (ginseng), a food homology and well-known medicinal herb. In this review, we summarize the current therapeutic effects and molecular mechanisms of ginsenosides in respiratory diseases. METHODS The reviewed studies were retrieved via a thorough analysis of numerous articles using electronic search tools including Sci-Finder, ScienceDirect, PubMed, and Web of Science. The following keywords were used for the online search: ginsenosides, asthma, influenza, pneumonia, chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung fibrosis, lung cancer, and clinical trials. We summarized the findings and the conclusions from 176 manuscripts on ginsenosides, including research articles and reviews. RESULTS Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK, which are the most commonly reported ginsenosides for treating of respiratory diseases, and other ginsenosides such as Rh1, Rk1, Rg5, Rd and Re, all primarily reduce pneumonia, fibrosis, and inhibit tumor progression by targeting NF-κB, TGF-β/Smad, PI3K/AKT/mTOR, and JNK pathways, thereby ameliorating respiratory diseases. CONCLUSION This review provides novel ideas and important aspects for the future research of ginsenosides for treating respiratory diseases.
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Zhao X, Wu J, Guo D, Hu S, Chen X, Hong L, Wang J, Ma J, Jiang Y, Niu T, Miao F, Li W, Wang B, Chen X, Song Y. Dynamic ginsenoside-sheltered nanocatalysts for safe ferroptosis-apoptosis combined therapy. Acta Biomater 2022; 151:549-560. [PMID: 36007778 DOI: 10.1016/j.actbio.2022.08.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/07/2022] [Accepted: 08/15/2022] [Indexed: 11/26/2022]
Abstract
Chemodynamic therapy (CDT)-activated apoptosis is a potential anticancer strategy. However, CDT encounters a bottleneck in clinical translation due to its serious side effects and low efficacy. Here, we first reveal that surface engineering of ginsenoside Rg3 dramatically alters the organ distribution and tumor enrichment of systematically administered nanocatalysts using the orthotopic pancreatic tumor model while avoiding toxicity and increasing efficacy in vivo to address the key and universal toxicity problems encountered in nanomedicine. Compared with nanocatalysts alone, Rg3-sheltered dynamic nanocatalysts form hydrophilic nanoclusters, prolonging their circulation lifespan in the blood, protecting the internal nanocatalysts from leakage while allowing their specific release at the tumor site. Moreover, the nanoclusters provide a drug-loading platform for Rg3 so that more Rg3 reaches the tumor site to achieve obvious synergistic effect with nanocatalysts. Rg3-sheltered dynamic nanocatalysts can simultaneously activate ferroptosis and apoptosis to significantly improve anticancer efficacy. Systematic administration of ginsenoside Rg3-sheltered nanocatalysts inhibited 86.6% of tumor growth without toxicity and prolonged the survival time of mice. This study provides a promising approach of nanomedicine with high biosafety and a new outlook for catalytic ferroptosis-apoptosis combined antitumor therapies. STATEMENT OF SIGNIFICANCE: : Chemodynamic therapy (CDT) has limited clinical efficacy in cancer. In this study, we developed Rg3-sheltered dynamic nanocatalysts, which could simultaneously activate ferroptosis based on CDT-activated apoptosis, and ultimately form a combined therapy of ferroptosis-apoptosis to kill tumors. Studies have shown that the nanocatalysts after Rg3 surface engineering dramatically alters the pharmacokinetics and organ distribution of the nanocatalysts after being systematically administered, resulting in avoiding the toxicity of the nanocatalysts. Nanocatalysts also act as a drug-loading platform, guiding more Rg3 into the tumor site. This study emphasizes that nanocatalysts after Rg3 surface engineering improve the safety and effectiveness of ferroptosis-apoptosis combined therapy, providing an effective idea for clinical practices.
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Affiliation(s)
- Xiaoxiong Zhao
- Center of Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China
| | - Jicheng Wu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China
| | - Danjing Guo
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shen Hu
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Xiang Chen
- Eye Center, the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009 China
| | - Liangjie Hong
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Junmei Wang
- Center of Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China
| | - Jugang Ma
- Center of Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China
| | - Yangkang Jiang
- Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China
| | - Tianye Niu
- Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China
| | - Fenglin Miao
- Department of Hepatobiliary and Transplantation Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361005, China
| | - Wengang Li
- Department of Hepatobiliary and Transplantation Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361005, China
| | - Ben Wang
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China; Cancer Center, Zhejiang University, Hangzhou 310029, China
| | - Xinhua Chen
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310003, China; Zhejiang Key Laboratory for Pulsed Power Technology Translational Medicine, Hangzhou 310000, China.
| | - Yujun Song
- Center of Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China; Zhejiang Key Laboratory for Pulsed Power Technology Translational Medicine, Hangzhou 310000, China; Zhengzhou Tianzhao Biomedical Technology Company Ltd., 7 Dongqing Street, Zhengzhou High Tech Development Zone, Zhengzhou 451450, China.
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Namwan N, Senawong G, Phaosiri C, Kumboonma P, Somsakeesit LO, Samankul A, Leerat C, Senawong T. HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells. Molecules 2022; 27:4014. [PMID: 35807258 PMCID: PMC9268269 DOI: 10.3390/molecules27134014] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/19/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
Previous research reported that the curcumin derivative (CU17) inhibited several cancer cell growths in vitro. However, its anticancer potential against human lung cancer cells (A549 cell lines) has not yet been evaluated. The purpose of this research was to examine the HDAC inhibitory and anti-cancer activities of CU17 compared to curcumin (CU) in A549 cells. An in vitro study showed that CU17 had greater HDAC inhibitory activity than CU. CU17 inhibited HDAC activity in a dose dependent manner with the half-maximal inhibitory concentration (IC50) value of 0.30 ± 0.086 µg/mL against HDAC enzymes from HeLa nuclear extract. In addition, CU17 could bind at the active pockets of both human class I HDACs (HDAC1, 2, 3, and 8) and class II HDACs (HDAC4, 6, and 7) demonstrated by molecular docking studies, and caused hyperacetylation of histone H3 (Ac-H3) in A549 cells shown by Western blot analysis. MTT assay indicated that both CU and CU17 suppressed A549 cell growth in a dose- and time-dependent manner. Besides, CU and CU17 induced G2/M phase cell cycle arrest and p53-independent apoptosis in A549 cells. Both CU and CU17 down-regulated the expression of p53, p21, Bcl-2, and pERK1/2, but up-regulated Bax expression in this cell line. Although CU17 inhibited the growth of lung cancer cells less effectively than CU, it showed less toxicity than CU for non-cancer cells. Accordingly, CU17 is a promising agent for lung cancer treatment. Additionally, CU17 synergized the antiproliferative activity of Gem in A549 cells, indicating the possibility of employing CU17 as an adjuvant treatment to enhance the chemotherapeutic effect of Gem in lung cancer.
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Affiliation(s)
- Narissara Namwan
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; (N.N.); (G.S.); (A.S.); (C.L.)
| | - Gulsiri Senawong
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; (N.N.); (G.S.); (A.S.); (C.L.)
| | - Chanokbhorn Phaosiri
- Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Pakit Kumboonma
- Department of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima 30000, Thailand;
| | - La-or Somsakeesit
- Department of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan, Khon Kaen 40000, Thailand;
| | - Arunta Samankul
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; (N.N.); (G.S.); (A.S.); (C.L.)
| | - Chadaporn Leerat
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; (N.N.); (G.S.); (A.S.); (C.L.)
| | - Thanaset Senawong
- Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; (N.N.); (G.S.); (A.S.); (C.L.)
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Yan L, Sundaram S, Rust BM, Picklo MJ, Bukowski MR. Metabolomes of Lewis lung carcinoma metastases and normal lung tissue from mice fed different diets. J Nutr Biochem 2022; 107:109051. [DOI: 10.1016/j.jnutbio.2022.109051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/02/2022] [Accepted: 04/17/2022] [Indexed: 12/20/2022]
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Fu L, Zhang W, Zhou X, Fu J, He C. Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma. Bioact Mater 2022; 17:221-233. [PMID: 35386464 PMCID: PMC8965157 DOI: 10.1016/j.bioactmat.2022.01.035] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/11/2022] [Accepted: 01/19/2022] [Indexed: 02/09/2023] Open
Abstract
Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment. Although nanotechnology is widely applied in cancer therapy, poor targeting and inadequate efficiency hinder its development. In this study, we prepared alendronate (ALD)/K7M2 cell membranes-coated hollow manganese dioxide (HMnO2) nanoparticles as a nanocarrier to load Ginsenoside Rh2 (Rh2) for Magnetic Resonance imaging (MRI)-guided immuno-chemodynamic combination osteosarcoma therapy. Subsequently, the ALD and K7M2 cell membranes were successively modified on the surface of HMnO2 and loaded with Rh2. The tumor microenvironment (TME)-activated Rh2@HMnO2-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities, excellent GSH-sensitive drug release profile and MRI capability, and attractive immuno-chemodynamic combined therapeutic efficiency. The Rh2@HMnO2-AM nanoparticles can effectively trigger immunogenic cell death (ICD), activate CD4+/CD8+ T cells in vivo, and upregulate BAX, BCL-2 and Caspase-3 in cellular level. Further results revealed that Rh2@HMnO2-AM enhanced the secretion of IL-6, IFN-γ and TNF-α in serum and inhibited the generation of FOXP3+ T cells (Tregs) in tumors. Moreover, the Rh2@HMnO2-AM treatment significant restricted tumor growth in-situ tumor-bearing mice. Therefore, Rh2@HMnO2-AM may serve as an effective and bio-friendly nanoparticle platform combined with immunotherapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.
Ginsenoside Rh2 was loaded in Hollow MnO2 NPs for enhancing its bioavailability. The orthotopic tumor model exhibits a convincing therapeutic effect of nanosystems. Alendronate/cell membranes enhance osteosarcoma targeting and tumor-homing ability. Tumor microenvironment-induced NPs degradation can release immune stimulant and Mn2+. The NPs had excellent immuno-chemodynamic combination osteosarcoma therapy effect.
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Affiliation(s)
- Liwen Fu
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China
| | - Weiying Zhang
- Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China
| | - Xiaojun Zhou
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China
| | - Jingzhong Fu
- Department of Thoracic Oncology, Jiujiang Cancer Hospital, Jiangxi Province, China
| | - Chuanglong He
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China
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LI H, WANG T, CUI W, GAO Z, CHE Z. Effect of ginsenoside Rg3 on proliferation and apoptosis of 786-0 cells and AktmTORSTAT3 signaling in renal carcinoma. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.124121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Affiliation(s)
| | | | - Wei CUI
- Zibo Central Hospital, China
| | | | - Zi CHE
- Zibo Central Hospital, China
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The Effect of Terpenoid Natural Chinese Medicine Molecular Compound on Lung Cancer Treatment. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:3730963. [PMID: 34956377 PMCID: PMC8702311 DOI: 10.1155/2021/3730963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/18/2021] [Accepted: 12/01/2021] [Indexed: 12/18/2022]
Abstract
Among all malignant tumors in the whole universe, the incidence and mortality of lung cancer disease rank first. Especially in the past few years, the occurrence of lung cancer in the urban population has continued to increase, which seriously threatens the lives and health of people. Among the many treatments for lung cancer, chemotherapy is the best one, but traditional chemotherapy has low specificity and drug resistance. To address the above issue, this study reviews the five biological pathways that common terpenoid compounds in medicinal plants interfere with the occurrence and development of lung cancer: cell proliferation, cell apoptosis, cell autophagy, cell invasion, metastasis, and immune mechanism regulation. In addition, the mechanism of the terpenoid natural traditional Chinese medicine monomer compound combined with Western medicine in the multipathway antilung cancer is summarized.
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Zhao X, Wu J, Zhang K, Guo D, Hong L, Chen X, Wang B, Song Y. The synthesis of a nanodrug using metal-based nanozymes conjugated with ginsenoside Rg3 for pancreatic cancer therapy. NANOSCALE ADVANCES 2021; 4:190-199. [PMID: 36132964 PMCID: PMC9419118 DOI: 10.1039/d1na00697e] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 10/20/2021] [Indexed: 05/10/2023]
Abstract
Nanozymes have limited applications in clinical practice due to issues relating to their safety, stability, biocompatibility, and relatively low catalytic activity in the tumor microenvironment (TME) in vivo. Herein, we report a synergistic enhancement strategy involving the conjugation of metal-based nanozymes (Fe@Fe3O4) with natural bioactive organic molecules (ginsenoside Rg3) to establish a new nanodrug. Importantly, this metal-organic nanocomposite drug ensured the stability and biosafety of the nanozyme cores and the cellular uptake efficiency of the whole nanodrug entity. This nanodrug is based on integrating the biological characteristics and intrinsic physicochemical properties of bionics. The glycoside chain of Rg3 forms a hydrophilic layer on the outermost layer of the nanodrug to improve the biocompatibility and pharmacokinetics. Additionally, Rg3 can activate apoptosis and optimize the activity and status of normal cells. Internal nanozymes enter the TME and release Fe3+ and Fe2+, and the central metal Fe(0) continuously generates highly active Fe2+ under the conditions of the TME and in the presence of Fe3+, maintaining the catalytic activity. Therefore, these nanozymes can effectively produce reactive oxygen species and oxygen in the TME, thereby promoting the apoptosis of cancer cells. Thus, we propose the use of a new type of metal-organic nanocomposite material as a synergistic strategy against cancer.
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Affiliation(s)
- Xiaoxiong Zhao
- Center for Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing Beijing 100083 China
- Zhejiang Key Laboratory for Pulsed Power Technology Translational Medicine Hangzhou 310000 China
| | - Jicheng Wu
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310009 China
- Institute of Translational Medicine, Zhejiang University Hangzhou 310029 China
| | - Kaixin Zhang
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310009 China
- Institute of Translational Medicine, Zhejiang University Hangzhou 310029 China
| | - Danjing Guo
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003 China
| | - Liangjie Hong
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003 China
| | - Xinhua Chen
- Zhejiang Key Laboratory for Pulsed Power Technology Translational Medicine Hangzhou 310000 China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003 China
| | - Ben Wang
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310009 China
- Institute of Translational Medicine, Zhejiang University Hangzhou 310029 China
| | - Yujun Song
- Center for Modern Physics Technology, School of Mathematics and Physics, University of Science and Technology Beijing Beijing 100083 China
- Zhejiang Key Laboratory for Pulsed Power Technology Translational Medicine Hangzhou 310000 China
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Ji D, Fleig A, Horgen FD, Feng ZP, Sun HS. Modulators of TRPM7 and its potential as a drug target for brain tumours. Cell Calcium 2021; 101:102521. [PMID: 34953296 DOI: 10.1016/j.ceca.2021.102521] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 12/14/2022]
Abstract
TRPM7 is a non-selective divalent cation channel with an alpha-kinase domain. Corresponding with its broad expression, TRPM7 has a role in a wide range of cell functions, including proliferation, migration, and survival. Growing evidence shows that TRPM7 is also aberrantly expressed in various cancers, including brain cancers. Because ion channels have widespread tissue distribution and result in extensive physiological consequences when dysfunctional, these proteins can be compelling drug targets. In fact, ion channels comprise the third-largest drug target type, following enzymes and receptors. Literature has shown that suppression of TRPM7 results in inhibition of migration, invasion, and proliferation in several human brain tumours. Therefore, TRPM7 presents a potential target for therapeutic brain tumour interventions. This article reviews current literature on TRPM7 as a potential drug target in the context of brain tumours and provides an overview of various selective and non-selective modulators of the channel relevant to pharmacology, oncology, and ion channel function.
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Affiliation(s)
- Delphine Ji
- Department of Surgery, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
| | - Andrea Fleig
- Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine and Cancer Center at the University of Hawaii, Honolulu, Hawaii 96813, USA
| | - F David Horgen
- Department of Natural Sciences, Hawaii Pacific University, Kaneohe, Hawaii 96744, USA
| | - Zhong-Ping Feng
- Department of Physiology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
| | - Hong-Shuo Sun
- Department of Surgery, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Department of Pharmacology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, Canada M5S 3M2.
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Radha Abbas Hasoon M, Jawad Kadhim N. Improvement of the Selectivity Index (SI) and Cytotoxicity Activity of Doxorubicin Drug by Panax ginseng Plant Extract. ARCHIVES OF RAZI INSTITUTE 2021; 76:659-666. [PMID: 34824758 PMCID: PMC8605847 DOI: 10.22092/ari.2021.355413.1681] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 08/05/2021] [Indexed: 01/24/2023]
Abstract
In China, Japan, and Korea, Panax ginseng has been used in traditional medicine for thousands of years. Panax is a plant used as a general tonic or adaptogen for chronically ill patients. The current study evaluated the cytotoxicity of Panax ginseng extract (PGE). Different cell lines (HCT-116, LNCaP, and normal cell line VERO) were treated with different inhibitory agentsat different concentrations (1000, 500, 250, 125, 62.5, and 31.25 µg/ml) as follows: G1 (Methanol Panax ginseng extract, PGE), G2 (Doxorubicin, DOX), and G3 (Methanol Panax ginseng extract +DOX, PDD). Each inhibitory agent group was used to treat the cancerous cell lines HCT-116, LNCaP, and normal cell line (VERO) to obtain IC50% by MTT assay. The inhibitory ability of the 1000 μg/ml PGE was significantly increased in all the three-cell lines compared with other concentrations. The recorded data revealed that the inhibition ability of PGE and Doxorubicin towards the HCT-116 cell line significantly increased compared with the other cell lines. The interaction between different PGE concentrations and cell lines showed that the 1000 μg/ml PEG had the highest inhibitory effects on HCT-116 compared with other combinations. The interaction between different DOX concentrations and different types of cell lines showed that the 1000 μg/ml DOX had the highest inhibitory effects on LNCap compared with other combinations. The PGD inhibition ability reflected a significantly higher difference toward the HCT-116 cell line as compared with other cell lines. IC50% is the concentrations (µg/ml) to kill 50% of cell line. It was calculated by MTT assay for three cell lines: HCT-116, LNCaP, and VERO. The rate of effectiveness of the inhibitory factors (PGE, DOX, and PGD) showed highly significant differences toward the cell line HCT-116 compared to the other cell lines. This indicates the safety of the PGE compound and its low toxicity toward normal cells, quite the opposite of cancer cells as compared to the common drug DOX and combined PGD (PGE+DOX). PGD combined with DOX (PGE + DOX) showed antagonistic results toward the HCT116, LNCaP, and VERO cell lines, while UDE combined with DOX (UDE+DOX) showed synergistic activity.
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Affiliation(s)
| | - N Jawad Kadhim
- University of Kufa, Faculty of Science, Department of Biology, Iraq
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Zhu Y, Liang J, Gao C, Wang A, Xia J, Hong C, Zhong Z, Zuo Z, Kim J, Ren H, Li S, Wang Q, Zhang F, Wang J. Multifunctional ginsenoside Rg3-based liposomes for glioma targeting therapy. J Control Release 2021; 330:641-657. [DOI: 10.1016/j.jconrel.2020.12.036] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 12/12/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022]
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Ratan ZA, Youn SH, Kwak YS, Han CK, Haidere MF, Kim JK, Min H, Jung YJ, Hosseinzadeh H, Hyun SH, Cho JY. Adaptogenic effects of Panax ginseng on modulation of immune functions. J Ginseng Res 2021; 45:32-40. [PMID: 33437154 PMCID: PMC7790873 DOI: 10.1016/j.jgr.2020.09.004] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 09/02/2020] [Accepted: 09/11/2020] [Indexed: 12/14/2022] Open
Abstract
Traditional medicinal practices have used natural products such as adaptogens to treat inflammatory, autoimmune, neurodegenerative, bacterial, and viral diseases since the early days of civilization. Panax ginseng Myer is a common herb used in East Asian countries for millennia, especially in Korea, China, and Japan. Numerous studies indicate that ginseng can modulate the immune system and thereby prevent diseases. Although the human immune system comprises many different types of cells, multiple studies suggest that each type of immune cell can be controlled or stimulated by ginseng or its derivatives. Provisional lists of ginseng's potential for use against viruses, bacteria, and other microorganisms suggest it may prove to be a valuable pharmaceutical resource, particularly if higher-quality evidence can be found. Here, we reviewed the role of ginseng as an immune-modulating agent in attempt to provide a valuable starting point for future studies on the herb and the human immune system.
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Affiliation(s)
- Zubair Ahmed Ratan
- School of Health and Society, University of Wollongong, NSW, Australia
- Department of Biomedical Engineering, Khulna University of Engineering and Technology, Khulna, Bangladesh
| | - Soo Hyun Youn
- R&D Headquarters, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Yi-Seong Kwak
- R&D Headquarters, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Chang-Kyun Han
- R&D Headquarters, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | | | - Jin Kyeong Kim
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea
| | - Hyeyoung Min
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
| | - You-Jung Jung
- Biological Resources Utilization Department, National Institute of Biological Resources, Incheon, Republic of Korea
| | | | - Sun Hee Hyun
- R&D Headquarters, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Jae Youl Cho
- Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea
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Yoon SJ, Kim SK, Lee NY, Choi YR, Kim HS, Gupta H, Youn GS, Sung H, Shin MJ, Suk KT. Effect of Korean Red Ginseng on metabolic syndrome. J Ginseng Res 2020; 45:380-389. [PMID: 34025131 PMCID: PMC8134847 DOI: 10.1016/j.jgr.2020.11.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 09/24/2020] [Accepted: 11/02/2020] [Indexed: 12/27/2022] Open
Abstract
Metabolic syndrome (MS) refers to a clustering of at least three of the following medical conditions: high blood pressure, abdominal obesity, hyperglycemia, low high-density lipoprotein level, and high serum triglycerides. MS is related to a wide range of diseases which includes obesity, diabetes, insulin resistance, cardiovascular disease, dyslipidemia, or non-alcoholic fatty liver disease. There remains an ongoing need for improved treatment strategies for MS. The most important risk factors are dietary pattern, genetics, old age, lack of exercise, disrupted biology, medication usage, and excessive alcohol consumption, but pathophysiology of MS has not been completely identified. Korean Red Ginseng (KRG) refers to steamed/dried ginseng, traditionally associated with beneficial effects such as anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. KRG has been often used in traditional medicine to treat multiple metabolic conditions. This paper summarizes the effects of KRG in MS and related diseases such as obesity, cardiovascular disease, insulin resistance, diabetes, dyslipidemia, or non-alcoholic fatty liver disease based on experimental research and clinical studies.
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Key Words
- ACC, Acetyl-Coenzyme A carboxylase
- ADP, adenosine diphosphate
- AG, American ginseng extract
- AGE, advanced glycation end product
- ALT, alanine aminotransferase
- AMPK, AMP-activated protein kinase
- AST, aspartate aminotransferase
- Akt, protein kinase B
- BMI, body mass index
- C/EBPα, CCAAT/enhancer-binding protein alpha
- COX-2, cyclooxygenase-2
- CPT, current perception threshold
- CPT-1, carnitine palmitoyl transferase 1
- CRP, C-reactive protein
- CVD, Cardiovascular disease
- DBP, diastolic blood pressure
- DEN, diethyl nitrosamine
- EAT, epididymis adipose tissue
- EF, ejection fraction
- FABP4, fatty acid binding protein 4
- FAS, Fatty acid synthase
- FFA, free fatty acid
- FR, fine root concentration
- FS, fractional shortening
- GBHT, ginseng-plus-Bai-Hu-Tang
- GLUT, glucose transporter type
- GPx, glutathione peroxidase
- GS, ginsenoside
- GST, glutathione S-transferase
- GST-P, glutathione S-transferase placental form
- GTT, glucose tolerance test
- HCC, hepatocellular carcinoma
- HCEF-RG, hypotensive components-enriched fraction of red ginseng
- HDL, high-density lipoprotein
- HFD, High fat diet
- HOMA-IR, homeostasis model assessment of insulin resistance index
- HbA1c, glycosylated hemoglobin
- I.P., intraperitoneal injection
- IL, interleukin
- IR, insulin resistance
- ITT, insulin tolerance test
- Insulin resistance
- KRG, Korean Red Ginseng
- LDL, low-density lipoprotein
- LPL, lipoprotein lipase
- Lex, lower extremities
- MDA, malondialdehyde
- MMP, Matrix metallopeptidases
- MS, Metabolic syndrome
- Metabolic syndrome
- NAFLD, Non-alcoholic fatty liver disease
- NF-кB, nuclear factor kappa-light-chain-enhancer of activated B cells
- NK cell, Natural killer cell
- NMDA-NR1, N-methyl-D-aspartate NR1
- NO, nitric oxide
- NRF1, Nuclear respiratory factor 1
- Non-alcoholic fatty liver disease
- Nrf2, Nuclear factor erythroid 2-related factor 2
- OLETF rat, Otsuka Long-Evans Tokushima fatty rat
- PCG-1α, PPAR-γ coactivator-1α
- PI3K, phosphoinositide 3-kinase
- PPAR, peroxisome proliferator-activated receptors
- PPD, protopanaxadiol
- PPT, protopanaxatriol
- Panax ginseng
- REKRG, Rg3-enriched KRG
- ROS, Reactive oxygen species
- Rg3-KGE, Rg3-enriched KRG extract
- SBP, systolic blood pressure
- SCD, Stearoyl-Coenzyme A desaturase
- SHR, spontaneously hypertensive rat
- SREBP-1C, Sterol regulatory element-binding protein 1
- STAT5, Signal transducer and activator of transcription 5
- STZ, streptozotocin
- TBARS, thiobarbituric acid reactive substances
- TC, total cholesterol
- TG, triglyceride
- TNF, tumor necrosis factor
- UCP, Mitochondrial uncoupling proteins
- VLDL, very low-density lipoprotein
- iNOS, inducible nitric oxide synthase
- t-BHP, tert-butyl hyperoxide
- tGST, total glutathione
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Affiliation(s)
- Sang Jun Yoon
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Seul Ki Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Na Young Lee
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Ye Rin Choi
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Hyeong Seob Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Haripriya Gupta
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Gi Soo Youn
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Hotaik Sung
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Min Jea Shin
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
| | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea
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Anti-Angiogenic Properties of Ginsenoside Rg3. Molecules 2020; 25:molecules25214905. [PMID: 33113992 PMCID: PMC7660320 DOI: 10.3390/molecules25214905] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022] Open
Abstract
Ginsenoside Rg3 (Rg3) is a member of the ginsenoside family of chemicals extracted from Panax ginseng. Like other ginsenosides, Rg3 has two epimers: 20(S)-ginsenoside Rg3 (SRg3) and 20(R)-ginsenoside Rg3 (RRg3). Rg3 is an intriguing molecule due to its anti-cancer properties. One facet of the anti-cancer properties of Rg3 is the anti-angiogenic action. This review describes the controversies on the effects and effective dose range of Rg3, summarizes the evidence on the efficacy of Rg3 on angiogenesis, and raises the possibility that Rg3 is a prodrug.
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Hong S, Cai W, Huang Z, Wang Y, Mi X, Huang Y, Lin Z, Chen X. Ginsenoside Rg3 enhances the anticancer effect of 5‑FU in colon cancer cells via the PI3K/AKT pathway. Oncol Rep 2020; 44:1333-1342. [PMID: 32945504 PMCID: PMC7448421 DOI: 10.3892/or.2020.7728] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 09/13/2019] [Indexed: 12/12/2022] Open
Abstract
Chemotherapy is one of the most commonly used treatments for patients with advanced colon cancer, yet the toxicity of chemotherapy agents, such as 5‑fluorouracil (5‑FU), limits the effectiveness of chemotherapy. Ginsenoside Rg3 (Rg3) is an active ingredient isolated from ginseng. Rg3 has been shown to display anticancer effects on a variety of malignancies. Yet, whether Rg3 synergizes the effect of 5‑FU to inhibit the growth of human colon cancer remains unknown. The present study was designed to ascertain whether Rg3 is able to enhance the anti‑colon cancer effect of 5‑FU. The results revealed that combined treatment of Rg3 and 5‑FU significantly enhanced the inhibition of the proliferation, colony formation, invasion and migration of human colon cancer cells (SW620 and LOVO) in vitro. We also found that combined treatment of Rg3 and 5‑FU significantly enhanced the apoptosis of colon cancer cells by activating the Apaf1/caspase 9/caspase 3 pathway and arrested the cell cycle of the colon cancer cells in G0/G1 by promoting the expression of Cyclin D1, CDK2 and CDK4. In addition, the PI3K/AKT signaling pathway in colon cancer cells was suppressed by Rg3 and 5‑FU. In vivo, Rg3 synergized the effect of 5‑FU to inhibit the growth of human colon cancer xenografts in nude mice. Similarly, combined treatment of Rg3 and 5‑FU altered the expression of colon cancer protein in vivo and in vitro. Collectively, the present study demonstrated that ginsenoside Rg3 enhances the anticancer effect of 5‑FU in colon cancer cells via the PI3K/AKT pathway.
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Affiliation(s)
- Shunzhong Hong
- Endoscopy Center, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Wenjie Cai
- Department of Tumor Radiotherapy, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Zicheng Huang
- Department of Gastroenterology, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Yubin Wang
- Department of Gastroenterology, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Xifeng Mi
- Endoscopy Center, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Yisen Huang
- Department of Gastroenterology, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Zhijin Lin
- Department of Gastroenterology, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Xiangbo Chen
- Endoscopy Center, The Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
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Ginsenoside Rg1 Drives Stimulations of Timosaponin AIII-Induced Anticancer Effects in Human Osteosarcoma Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8980124. [PMID: 32774433 PMCID: PMC7396057 DOI: 10.1155/2020/8980124] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 06/27/2020] [Indexed: 12/27/2022]
Abstract
A ginsenoside Rg1 is an active compound extracted from the stem and/or root of ginseng. Rg1 has been known to affect various human organ systems including the immune, cardiovascular, and nervous systems with its pharmacological effects. Timosaponin AIII (TA3) is a type of spirostanol saponins that are the major compounds of Anemarrhena asphodeloides. TA3 exerts anticancer effects in various human cancers, and the effects include attenuations of cancer cell migration and induction of apoptosis. In this study, I report that Rg1 drives the stimulation of TA3-induced cytotoxic effects in MG63 human osteosarcoma cells. Rg1 stimulates TA3-induced apoptosis in MG63 cells via selective intensification of caspase-3 activation. Rg1 and TA3 synergistically induced antimetastatic effects such as attenuation of MG63 cell migration and inhibitions of matrix metalloproteinases (MMP-2 and MMP-9). Rg1 and TA3 synergistically suppressed JNK, p38, ERK, β-catenin, and CREB signaling, which are key regulators of cancer metastasis. Finally, the synergistic anticancer effects of Rg1 and TA3 were also observed in U2OS human osteosarcoma cells, and this may indicate that the synergy is not limited specifically to MG63 cells. The results presented here suggest that the combinatorial use of Rg1 and TA3 may be a promising way to develop an effective antiosteosarcoma agent.
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Zou J, Su H, Zou C, Liang X, Fei Z. Ginsenoside Rg3 suppresses the growth of gemcitabine-resistant pancreatic cancer cells by upregulating lncRNA-CASC2 and activating PTEN signaling. J Biochem Mol Toxicol 2020; 34:e22480. [PMID: 32104955 DOI: 10.1002/jbt.22480] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 01/22/2020] [Accepted: 02/14/2020] [Indexed: 12/11/2022]
Abstract
Pancreatic cancer is one of the most fatal malignancies with high mortality. Gemcitabine (GEM)-based chemotherapy is the most important treatment. However, the development of GEM resistance leads to chemotherapy failure. Previous studies demonstrated the anticancer activity of ginsenoside Rg3 in a variety of carcinomas through modulating multiple signaling pathways. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, flow cytometry apoptosis assay, Western blotting assay, xenograft experiment, and immunohistochemistry assay were performed in GEM-resistant pancreatic cancer cell lines. Ginsenoside Rg3 inhibited the viability of GEM-resistant pancreatic cancer cells in a time-dependent and concentration-dependent manner through induction of apoptosis. The level of long noncoding RNA cancer susceptibility candidate 2 (CASC2) and PTEN expression was upregulated by the ginsenoside Rg3 treatment, and CASC2/PTEN signaling was involved in the ginsenoside Rg3-induced cell growth suppression and apoptosis in GEM-resistant pancreatic cancer cells. Ginsenoside Rg3 could be an effective anticancer agent for chemoresistant pancreatic cancer.
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Affiliation(s)
- Jifeng Zou
- Department of Oncology, The First People's Hospital of Pinghu, Pinghu, China
| | - Huafang Su
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Changling Zou
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaodong Liang
- Department of Pathology, Yancheng Hospital Affiliated Southeast University, Yancheng, China
| | - Zhenghua Fei
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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30
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Lan Y, Li X, Liu Y, He Y, Hao C, Wang H, Jin L, Zhang G, Zhang S, Zhou A, Zhang L. Pingyangmycin inhibits glycosaminoglycan sulphation in both cancer cells and tumour tissues. J Cell Mol Med 2020; 24:3419-3430. [PMID: 32068946 PMCID: PMC7131950 DOI: 10.1111/jcmm.15017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 01/05/2020] [Accepted: 01/10/2020] [Indexed: 12/18/2022] Open
Abstract
Pingyangmycin is a clinically used anticancer drug and induces lung fibrosis in certain cancer patients. We previously reported that the negatively charged cell surface glycosaminoglycans are involved in the cellular uptake of the positively charged pingyangmycin. However, it is unknown if pingyangmycin affects glycosaminoglycan structures. Seven cell lines and a Lewis lung carcinoma‐injected C57BL/6 mouse model were used to understand the cytotoxicity of pingyangmycin and its effect on glycosaminoglycan biosynthesis. Stable isotope labelling coupled with LC/MS method was used to quantify glycosaminoglycan disaccharide compositions from pingyangmycin‐treated and untreated cell and tumour samples. Pingyangmycin reduced both chondroitin sulphate and heparan sulphate sulphation in cancer cells and in tumours. The effect was persistent at different pingyangmycin concentrations and at different exposure times. Moreover, the cytotoxicity of pingyangmycin was decreased in the presence of soluble glycosaminoglycans, in the glycosaminoglycan‐deficient cell line CHO745, and in the presence of chlorate. A flow cytometry‐based cell surface FGF/FGFR/glycosaminoglycan binding assay also showed that pingyangmycin changed cell surface glycosaminoglycan structures. Changes in the structures of glycosaminoglycans may be related to fibrosis induced by pingyangmycin in certain cancer patients.
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Affiliation(s)
- Ying Lan
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China.,College of Food Science and Engineering, Northwest A&F University, Yangling, China
| | - Xiulian Li
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yong Liu
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanli He
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cui Hao
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hua Wang
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Liying Jin
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Guoqing Zhang
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shufeng Zhang
- College of Chemistry, Tianjin Normal University, Tianjin, China
| | - Aimin Zhou
- Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH, USA
| | - Lijuan Zhang
- Systems Biology & Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China
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An X, Bao Q, Di S, Zhao Y, Zhao S, Zhang H, Lian F, Tong X. The interaction between the gut Microbiota and herbal medicines. Biomed Pharmacother 2019; 118:109252. [DOI: 10.1016/j.biopha.2019.109252] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 07/18/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022] Open
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Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis. Anal Cell Pathol (Amst) 2019; 2019:3815786. [PMID: 31534898 PMCID: PMC6732603 DOI: 10.1155/2019/3815786] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Accepted: 04/28/2019] [Indexed: 12/13/2022] Open
Abstract
Aim Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro. The aim of this study was to investigate the cross-link for apoptosis induction and antiangiogenesis effect of Rg3 on orthotopic HCC in vivo. Methods The murine HCC cells Hep1-6 were implanted in the liver of mouse. With oral feeding of Rg3 (10 mg/kg once a day for 30 days), the quantitative analysis of apoptosis was performed by using pathology and a transmission electron microscope and microvessel density was quantitatively measured by immunohistochemical staining of the CD105 antibody. The mice treated with Rg3 (n = 10) were compared with the control (n = 10) using Kaplan-Meier analysis. Animal weight and tumor weight were measured to determine the toxicity of Rg3 and antitumor effect on an orthotopic HCC tumor model. Results With oral feeding of Rg3 daily in the first 30 days on tumor implantation, Rg3 significantly decreased the orthotopic tumor growth and increased the survival of animals (P < 0.05). Rg3-treated mice showed a longer survival than the control (P < 0.05). Rg3 treatment induced apoptosis and inhibited angiogenesis. They contributed to the tumor shrinkage. Rg3 initialized the tumor apoptotic progress, which then weakened the tumor volume and its capability to produce the vascularized network for further growth of the tumor and remote metastasis. Conclusion Rg3 inhibited the activation of microtumor vessel formation in vivo besides its apoptosis induction. Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen.
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Yan H, Jin H, Fu Y, Yin Z, Yin C. Production of Rare Ginsenosides Rg3 and Rh2 by Endophytic Bacteria from Panax ginseng. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:8493-8499. [PMID: 31310523 DOI: 10.1021/acs.jafc.9b03159] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
The ginsenosides Rh2 and Rg3 induce tumor cell apoptosis, inhibit tumor cell proliferation, and restrain tumor invasion and metastasis. Despite Rh2 and Rg3 having versatile pharmacological activities, contents of them in natural ginseng are extremely low. To produce ginsenosides Rh2 and Rg3, the saponin-producing capacity of endophytic bacteria isolated from Panax ginseng was investigated. In this work, 81 endophytic bacteria isolates were taken from ginseng roots by tissue separation methods. Among them, strain PDA-2 showed the highest capacity to produce the rare ginsenosides; the concentrations of rare ginsenosides Rg3 and Rh2 reached 62.20 and 18.60 mg/L, respectively. On the basis of phylogenetic analysis, it was found that strain PDA-2 belongs to the genus Agrobacterium and was very close to Agrobacterium rhizogenes.
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Affiliation(s)
- Huayu Yan
- Department of Chemistry , Yanbian University , Yanji , Jilin 133002 , People's Republic of China
| | - Huding Jin
- Graduate School of Convergence Science and Technology , Seoul National University , Seoul 151-742 , South Korea
| | - Yu Fu
- Department of Chemistry , Yanbian University , Yanji , Jilin 133002 , People's Republic of China
- College of Chemistry and Life Science , Anshan Normal University , Anshan , Liaoning 114007 , People's Republic of China
| | - Zhenxing Yin
- Department of Chemistry , Yanbian University , Yanji , Jilin 133002 , People's Republic of China
| | - Chengri Yin
- Department of Chemistry , Yanbian University , Yanji , Jilin 133002 , People's Republic of China
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Xu T, Yang R, Ma X, Chen W, Liu S, Liu X, Cai X, Xu H, Chi B. Bionic Poly(γ-Glutamic Acid) Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars. Adv Healthc Mater 2019; 8:e1900123. [PMID: 30972958 DOI: 10.1002/adhm.201900123] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 03/15/2019] [Indexed: 12/16/2022]
Abstract
Hypertrophic scarring (HS) remains a great challenge in wound dressing. Although various bionic extracellular matrix (ECM) biomaterials have been designed towards HS treatment, not all biomaterials can synergize biological functions and application functions in wound repair. Bionic scar-inhibiting scaffolds, loaded with biomolecules or drugs, become promising strategies for scarless skin regeneration. In this work, inspired by the physicochemical environment of ECM, a versatile fabrication of poly(γ-glutamic acid) based on electrospun photocrosslinkable hydrogel fibrous scaffolds incorporated with ginsenoside Rg3 (GS-Rg3) is developed for tissue repair and wound therapy. Decorated with adhesive peptide, bionic fibrous scaffolds can accelerate fibroblasts to sprout and grow, forming organized space-filling basement that gradually fills a depression before wound close up in the early stage. Additionally, by sustained release of GS-Rg3 in late stage, fibrous scaffolds promote scarless wound healing in vivo as evidenced by the promotion of cell communication and skin regeneration, as well as the subsequent decrease of angiogenesis and collagen accumulation. These ECM-inspired fibrous scaffolds, therefore, offer new perspectives on accelerated wound healing and tissue regeneration.
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Affiliation(s)
- Tingting Xu
- State Key Laboratory of Materials‐Oriented Chemical EngineeringCollege of Food Science and Light IndustryNanjing Tech University Nanjing 211816 China
| | - Rong Yang
- State Key Laboratory of Materials‐Oriented Chemical EngineeringCollege of Food Science and Light IndustryNanjing Tech University Nanjing 211816 China
| | - Xuebin Ma
- School of Chemical EngineeringNanjing University of Science and Technology Nanjing 210094 China
| | - Wei Chen
- State Key Laboratory of Materials‐Oriented Chemical EngineeringCollege of Food Science and Light IndustryNanjing Tech University Nanjing 211816 China
| | - Shuai Liu
- School of Chemical EngineeringNanjing University of Science and Technology Nanjing 210094 China
| | - Xin Liu
- State Key Laboratory of Materials‐Oriented Chemical EngineeringCollege of Food Science and Light IndustryNanjing Tech University Nanjing 211816 China
| | - Xiaojun Cai
- College of Materials Science and EngineeringNanjing Tech University Nanjing 211816 Nanjing China
| | - Hong Xu
- State Key Laboratory of Materials‐Oriented Chemical EngineeringCollege of Food Science and Light IndustryNanjing Tech University Nanjing 211816 China
- Jiangsu National Synergetic Innovation Center for Advanced Materials Nanjing Tech University Nanjing 211816 China
| | - Bo Chi
- State Key Laboratory of Materials‐Oriented Chemical EngineeringCollege of Food Science and Light IndustryNanjing Tech University Nanjing 211816 China
- Jiangsu National Synergetic Innovation Center for Advanced Materials Nanjing Tech University Nanjing 211816 China
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Bian Y, An GJ, Kim K, Ngo T, Shin S, Bae ON, Lim KM, Chung JH. Ginsenoside Rg3, a component of ginseng, induces pro-thrombotic activity of erythrocytes via hemolysis-associated phosphatidylserine exposure. Food Chem Toxicol 2019; 131:110553. [PMID: 31163221 DOI: 10.1016/j.fct.2019.05.061] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/19/2019] [Accepted: 05/31/2019] [Indexed: 12/19/2022]
Abstract
Ginseng and its active gradient, ginsenoside Rg3 (Rg3), are widely used for a variety of health benefits, but concerns over their misuses are increasing. Previously, it has been reported that Rg3 can cause hemolysis, but its health outcome remains unknown. Here, we demonstrated that Rg3 could promote the procoagulant activity of erythrocytes through the process of hemolysis, ultimately leading to increased thrombosis. In freshly isolated human erythrocytes, Rg3 caused pore formation and fragmentation of the erythrocyte membrane. Confocal microscopy observation and flow cytometric analysis revealed that remnant erythrocyte fragments after the exposure to Rg3 expressed phosphatidylserine (PS), which can promote blood coagulation through providing assembly sites for coagulation complexes. Rat in vivo experiments further confirmed that intravenous administration of Rg3 produced PS-bearing erythrocyte debris and increased thrombosis. Collectively, we demonstrated that Rg3 could induce the procoagulant activity of erythrocytes by generating PS-bearing erythrocyte debris through hemolysis, which might provoke thrombosis.
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Affiliation(s)
- Yiying Bian
- College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
| | - Gwang-Jin An
- College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
| | - Keunyoung Kim
- College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
| | - Thien Ngo
- College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
| | - Sue Shin
- Department of Laboratory Medicine, Boramae Hospital, Seoul, 156-707, South Korea.
| | - Ok-Nam Bae
- College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 426-791, South Korea.
| | - Kyung-Min Lim
- College of Pharmacy, Ewha Womans University, Seoul, 03760, South Korea.
| | - Jin-Ho Chung
- College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
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Metwaly AM, Lianlian Z, Luqi H, Deqiang D. Black Ginseng and Its Saponins: Preparation, Phytochemistry and Pharmacological Effects. Molecules 2019; 24:E1856. [PMID: 31091790 PMCID: PMC6572638 DOI: 10.3390/molecules24101856] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 05/12/2019] [Accepted: 05/13/2019] [Indexed: 01/19/2023] Open
Abstract
Black ginseng is a type of processed ginseng that is prepared from white or red ginseng by steaming and drying several times. This process causes extensive changes in types and amounts of secondary metabolites. The chief secondary metabolites in ginseng are ginsenosides (dammarane-type triterpene saponins), which transform into less polar ginsenosides in black ginseng by steaming. In addition, apparent changes happen to other secondary metabolites such as the increase in the contents of phenolic compounds, reducing sugars and acidic polysaccharides in addition to the decrease in concentrations of free amino acids and total polysaccharides. Furthermore, the presence of some Maillard reaction products like maltol was also engaged. These obvious chemical changes were associated with a noticeable superiority for black ginseng over white and red ginseng in most of the comparative biological studies. This review article is an attempt to illustrate different methods of preparation of black ginseng, major chemical changes of saponins and other constituents after steaming as well as the reported biological activities of black ginseng, its major saponins and other metabolites.
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Affiliation(s)
- Ahmed M Metwaly
- Liaoning University of Traditional Chinese Medicine, 77 Life one Road, DD port, Dalian Economic and Technical Development Zone, Dalian 116600, China.
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
| | - Zhu Lianlian
- Liaoning University of Traditional Chinese Medicine, 77 Life one Road, DD port, Dalian Economic and Technical Development Zone, Dalian 116600, China.
| | - Huang Luqi
- National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Mennei South street, Dong-Cheng District, Beijing 100700, China.
| | - Dou Deqiang
- Liaoning University of Traditional Chinese Medicine, 77 Life one Road, DD port, Dalian Economic and Technical Development Zone, Dalian 116600, China.
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Meng L, Ji R, Dong X, Xu X, Xin Y, Jiang X. Antitumor activity of ginsenoside Rg3 in melanoma through downregulation of the ERK and Akt pathways. Int J Oncol 2019; 54:2069-2079. [PMID: 31081060 PMCID: PMC6521931 DOI: 10.3892/ijo.2019.4787] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 04/02/2019] [Indexed: 12/13/2022] Open
Abstract
Advanced metastatic melanoma is a malignant tumor for which there is currently no effective treatment due to resistance development. Ginsenoside Rg3, a saponin component extracted from ginseng roots, has been shown to reduce melanoma cell proliferation by decreasing histone deacetylase 3 and increasing p53 acetylation. The availability of data on the role of Rg3 in melanoma is currently extremely limited. The aim of the present study was to further investigate the effects of Rg3 on B16 melanoma cells and the underlying molecular events. The findings demonstrated that Rg3 suppressed the proliferation and DNA synthesis of B16 cells. Rg3 exposure induced tumor cell cycle arrest at the S phase and reduced the expression of proliferating cell nuclear antigen (PCNA). Rg3 treatment also decreased metastasis of B16 cells in vitro and in vivo. The results indicated that this reduction was due to downregulation of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, Rg3 inhibited melanoma-induced angiogenesis, most likely by downregulating vascular endothelial growth factor (VEGF) in B16 cells. Rg3 exposure decreased the expression of VEGF in B16 cells and the VEGF downregulation further suppressed angiogenesis by attenuating the proliferation and migration of vascular endothelial cells. Finally, the western blotting data demonstrated that Rg3 reduced the expression of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in vitro and in vivo. This result indicated that the antimelanoma effects of Rg3 may be mediated through suppression of ERK and Akt signaling. Further research is required to assess the value of Rg3 as a novel therapeutic strategy for melanoma in the clinical setting.
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Affiliation(s)
- Lingbin Meng
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Rui Ji
- Department of Biology, Valencia College, Orlando, FL 32825, USA
| | - Xiaoming Dong
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xiaochun Xu
- Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xin Jiang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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Ma C, Guan H, Ju Z, Li S, Deng G, Zhang Y, Lin Q, Cheng X, Yang L, Wang Z, Wang C. Identification and characterization of forced degradation products and stability-indicating assay for notoginsenosidefc by using UHPLC-Q-TOF-MS and UHPLC-MS/MS: Insights into stability profile and degradation pathways. J Sep Sci 2019; 42:1550-1563. [DOI: 10.1002/jssc.201801295] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/05/2019] [Accepted: 02/10/2019] [Indexed: 12/27/2022]
Affiliation(s)
- Chao Ma
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Huida Guan
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Zhengcai Ju
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Shuping Li
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Gang Deng
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Yunpeng Zhang
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Qiyan Lin
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
| | - Xuemei Cheng
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
- Shanghai R&D Centre for Standardization of Chinese Medicines; Shanghai P. R. China
| | - Li Yang
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
- Shanghai R&D Centre for Standardization of Chinese Medicines; Shanghai P. R. China
| | - Zhengtao Wang
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
- Shanghai R&D Centre for Standardization of Chinese Medicines; Shanghai P. R. China
| | - Changhong Wang
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine; Shanghai P. R. China
- Shanghai R&D Centre for Standardization of Chinese Medicines; Shanghai P. R. China
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Ginsenoside Rg3 Inhibits Migration and Invasion of Nasopharyngeal Carcinoma Cells and Suppresses Epithelial Mesenchymal Transition. BIOMED RESEARCH INTERNATIONAL 2019; 2019:8407683. [PMID: 30915362 PMCID: PMC6409072 DOI: 10.1155/2019/8407683] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
Abstract
Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic head and neck cancer. Distant metastasis becomes the predominant mode of treatment failure in NPC patients. Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from traditional Chinese medicine ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 inhibits the migration and invasion activity of NPC cells and to explore the possible mechanisms. Our results revealed that Rg3 hampers cell migration and invasion in both HNE1 and CNE2 cell lines. A reduced level of matrix metalloproteinase-2 (MMP-2) and MMP-9 was induced by Rg3 treatment. In addition, Rg3 significantly altered the expression of epithelial mesenchymal transition (EMT) markers with increased E-cadherin but decreased Vimentin and N-cadherin expression. Transforming growth factor β- (TGF-β-) induced morphological transition and marker proteins change of EMT were reversed by Rg3. What is more, Rg3 suppressed the expression of EMT-related transcription factors, especially the Zinc Finger E-Box Binding Homeobox 1 (ZEB1). In summary, our data suggested that Rg3 could inhibit migration and invasion of NPC cells. This effect of Rg3 might be mediated through regulating MMP-2 and MMP-9 expressions and suppressing EMT. Thus, Rg3 may be a potentially effective agent for the treatment of NPC.
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Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer. MEDICINES 2019; 6:medicines6010017. [PMID: 30678106 PMCID: PMC6473622 DOI: 10.3390/medicines6010017] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 01/21/2019] [Accepted: 01/23/2019] [Indexed: 01/28/2023]
Abstract
Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-cancer treatment for breast cancer will be reviewed.
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So SH, Lee JW, Kim YS, Hyun SH, Han CK. Red ginseng monograph. J Ginseng Res 2018; 42:549-561. [PMID: 30337816 PMCID: PMC6190493 DOI: 10.1016/j.jgr.2018.05.002] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 04/12/2018] [Accepted: 05/08/2018] [Indexed: 12/22/2022] Open
Abstract
Ginseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.
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Affiliation(s)
- Seung-Ho So
- Laboratory of Fundamental Research, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Jong Won Lee
- Laboratory of Fundamental Research, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Young-Sook Kim
- Laboratory of Fundamental Research, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Sun Hee Hyun
- Laboratory of Fundamental Research, Korea Ginseng Corporation, Daejeon, Republic of Korea
| | - Chang-Kyun Han
- Laboratory of Fundamental Research, Korea Ginseng Corporation, Daejeon, Republic of Korea
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Sundaram S, Žáček P, Bukowski MR, Mehus AA, Yan L, Picklo MJ. Lipidomic Impacts of an Obesogenic Diet Upon Lewis Lung Carcinoma in Mice. Front Oncol 2018; 8:134. [PMID: 29868466 PMCID: PMC5958182 DOI: 10.3389/fonc.2018.00134] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/13/2018] [Indexed: 12/25/2022] Open
Abstract
Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Consumption of a high-fat obesogenic diet enhances spontaneous metastasis using a Lewis lung carcinoma (LLC) model. In order to gain further insights into the mechanisms by which dietary fats impact cancer progression, we conducted a lipidomic analysis of primary tumors originated from LLC from mice fed with a standard AIN93G diet or a soybean oil-based high-fat diet (HFD). Hierarchical clustering heatmap analysis of phosphatidylcholine (PC) lipids and phosphatidylethanolamine (PE) lipids demonstrated an increase in polyunsaturated fatty acids (PUFA)-containing phospholipids and a decrease in monounsaturated fatty acids (MUFA)-containing lipids in tumors from mice fed the HFD. The quantities of 51 PC and 24 PE lipids differed in primary tumors of LLC from mice fed the control diet and the HFD. Analysis of triacylglycerol (TAG) lipids identified differences in 32 TAG (by brutto structure) between the two groups; TAG analysis by neutral loss identified 46 PUFA-containing TAG species that were higher in mice fed with the HFD than in the controls. Intake of the HFD did not alter the expression of the de novo lipogenesis enzymes (fatty acid synthase, acetyl-CoA carboxylase-1, and stearoyl-CoA desaturase-1). Our results demonstrate that the dietary fatty acid composition of the HFD is reflected in the higher order lipidomic composition of primary tumors. Subsequent studies are needed to investigate how these lipidomic changes may be used for targeted dietary intervention to reduce tumor growth and malignant progression.
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Affiliation(s)
- Sneha Sundaram
- USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States
| | - Petr Žáček
- USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States
| | - Michael R Bukowski
- USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States
| | - Aaron A Mehus
- USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States
| | - Lin Yan
- USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States
| | - Matthew J Picklo
- USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States.,Department of Chemistry, University of North Dakota, Grand Forks, ND, United States
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Ginsenoside Rg3 Sensitizes Colorectal Cancer to Radiotherapy through Downregulation of Proliferative and Angiogenic Biomarkers. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:1580427. [PMID: 29743919 PMCID: PMC5878898 DOI: 10.1155/2018/1580427] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 12/27/2017] [Indexed: 01/09/2023]
Abstract
Background Radiation therapy is an important mode of colorectal cancer treatment. However, most people die of local recurrence after tumors become resistant to radiotherapy, and little progress has been made in treating radiotherapy-resistant colorectal cancer. Hence, novel agents that are nontoxic and can sensitize colorectal cancer to radiotherapy are urgently needed. Ginsenoside Rg3, a saponin extracted from ginseng, shows cytotoxicity against a variety of cancer cells through suppression of pathways linked to oncogenesis, including cell survival, proliferation, invasion, and angiogenesis. In this article, we investigated whether Rg3 can sensitize colorectal cancer to radiation in vivo. Methods and Materials We established CT-26 xenografts in BALB/c mice and treated them with vehicle, Rg3, radiation, and combined Rg3 + radiation. Mouse quality of life, survival, tumor volumes, and inhibitive rates were estimated. NF-κB activation was ascertained using electrophoretic mobility shift assay and immunohistochemistry. We also tested for markers of proliferation, angiogenesis, and invasion using immunohistochemistry and Western blot analysis. Results Rg3 significantly enhanced the efficacy of fractionated radiotherapy by improving the quality of life of mice. Moreover, tumors from mice xenografted with CT-26 cells and treated with combined Rg3 + radiotherapy showed significantly lower tumor volumes (P < 0.01 versus controls; P < 0.05 versus radiation alone), NF-κB activation, and expression of NF-κB-regulated gene products (cyclin D1, survivin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF)) compared with controls. The combination treatment was also effective in suppressing angiogenesis, as indicated by lower CD31+ microvessel density compared with controls (P < 0.05). Conclusion Our results suggest that Rg3 enhances the antitumor effects of radiotherapy for colorectal cancer by suppressing NF-κB and NF-κB-regulated gene products, leading to inhibition of tumors and prolongation of the lifespan of CT-26 xenograft BALB/c mice.
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Li Y, Wang Y, Niu K, Chen X, Xia L, Lu D, Kong R, Chen Z, Duan Y, Sun J. Clinical benefit from EGFR-TKI plus ginsenoside Rg3 in patients with advanced non-small cell lung cancer harboring EGFR active mutation. Oncotarget 2018; 7:70535-70545. [PMID: 27655708 PMCID: PMC5342572 DOI: 10.18632/oncotarget.12059] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 08/25/2016] [Indexed: 01/10/2023] Open
Abstract
Purpose Acquired resistance is a bottleneck that restricts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for lung cancer. Ginsenoside Rg3 is an antiangiogenic agent which can down-regulate the expressions of vascular endothelial growth factor (VEGF) and EGFR. Combination of EGFR-TKI and ginsenoside Rg3 may be a promising strategy to delay acquired resistance. This retrospective study explored the efficacy and safety of this combined regimen in patients with EGFR mutation and advanced non-small cell lung cancer (NSCLC). Results By the deadline of March 31th 2016, the median follow-up period reached 22.9 months. The median PFS was significantly longer in group A than in group B (12.4 months vs 9.9 months, P = 0.017). In addition, ORR was significantly higher in group A than in group B (59.6% vs 41.7%, P = 0.049). The median OS in group A showed no extended tendency compared with that in group B (25.4 months vs 21.4 months, P = 0.258). No significant difference in side effects was found between the two groups. Methods A total of 124 patients with advanced NSCLC and EGFR active mutation were collected and analyzed. All of them were treated with first-line EGFR-TKI and divided into two groups. In group A (n=52), patients were administered EGFR-TKI plus ginsenoside Rg3 at standard doses. In group B (n=72), patients received EGFR-TKI alone. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and side effects were analyzed. Conclusions Ginsenoside Rg3 improves median PFS and ORR of first-line EGFR-TKI treatment in EGFR-mutant advanced NSCLC patients, thus providing a new regimen to delay acquired resistance of EGFR-TKI.
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Affiliation(s)
- Yan Li
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Yanmei Wang
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Kai Niu
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Xiewan Chen
- Medical English Department, College of Basic Medicine, Third Military Medical University, Chongqing, 400038, China
| | - Liqin Xia
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Dingxi Lu
- Medical English Department, College of Basic Medicine, Third Military Medical University, Chongqing, 400038, China
| | - Rui Kong
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Zhengtang Chen
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Yuzhong Duan
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
| | - Jianguo Sun
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
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Abraham M, Augustine D, Rao RS, Sowmya SV, Haragannavar VC, Nambiar S, Prasad K, Awan KH, Patil S. Naturally Available Extracts Inhibiting Cancer Progression: A Systematic Review. J Evid Based Complementary Altern Med 2017; 22:870-878. [PMID: 29279018 PMCID: PMC5871319 DOI: 10.1177/2156587217744914] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Aim. This systematic review is aimed at evaluating the literature on the efficacy of naturally available extracts that inhibit cancer. Methods. A literature search was performed to strengthening the reporting of observational studies in epidemiology analysis. Approximately 3000 research articles were initially selected. Of these articles, 200 were included, and 2800 were excluded. On further scrutiny, 150 of the 200 studies were reviews, seminars, and presentations, and 50 were original study articles. Among these articles, 20 studies were selected for the systematic review. Results. The predominant molecular pathways followed by natural extracts were nuclear factor kappa B ligand, suppression of the protein kinase B-Akt/P13K pathway (an intracellular signaling pathway important in regulating cell cycle), vascular endothelial growth factor downregulation, and tumor protein-P53 tumor suppressor upregulation. Conclusions. It is evident that natural extracts have the ability to inhibit cancer progression. Continued research in this field could facilitate the use of natural extracts with currently available anticancer agents.
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Affiliation(s)
- Marin Abraham
- 1 Department of Oral and Maxillofacial Pathology, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - Dominic Augustine
- 1 Department of Oral and Maxillofacial Pathology, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - Roopa S Rao
- 1 Department of Oral and Maxillofacial Pathology, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - S V Sowmya
- 1 Department of Oral and Maxillofacial Pathology, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - Vanishri C Haragannavar
- 1 Department of Oral and Maxillofacial Pathology, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - Shwetha Nambiar
- 1 Department of Oral and Maxillofacial Pathology, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - Kavitha Prasad
- 2 Department of Oral and Maxillofacial Surgery, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
| | - Kamran Habib Awan
- 3 College of Dental Medicine, Roseman University of Health Sciences, South Jordan, Utah, USA
| | - Shankargouda Patil
- 4 Department of Maxillofacial Surgery and Diagnostic Science, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia
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Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of C/EBPβ/NF-κB signaling. Biomed Pharmacother 2017; 96:1240-1245. [DOI: 10.1016/j.biopha.2017.11.092] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/13/2017] [Accepted: 11/17/2017] [Indexed: 12/16/2022] Open
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Kim JH, Kim M, Yun SM, Lee S, No JH, Suh DH, Kim K, Kim YB. Ginsenoside Rh2 induces apoptosis and inhibits epithelial-mesenchymal transition in HEC1A and Ishikawa endometrial cancer cells. Biomed Pharmacother 2017; 96:871-876. [DOI: 10.1016/j.biopha.2017.09.033] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 09/05/2017] [Accepted: 09/08/2017] [Indexed: 12/13/2022] Open
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Kim SJ, Jang JY, Kim EJ, Cho EK, Ahn DG, Kim C, Park HS, Jeong SW, Lee SH, Kim SG, Kim YS, Kim HS, Kim BS, Lee JH, Siddiqui A. Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation. Hepatology 2017; 66:758-771. [PMID: 28329914 PMCID: PMC5755973 DOI: 10.1002/hep.29177] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 02/20/2017] [Accepted: 03/17/2017] [Indexed: 12/17/2022]
Abstract
UNLABELLED Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their use in treating patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine, and other conditions, which may be linked to mitochondrial dysfunction. Here, we show that clinically prescribed DAAs, including sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV-induced and DAA-induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only one of the compounds, ginsenoside Rg3 (G-Rg3), exhibited notable and promising anti-HCV potential. Treatment of HCV-infected cells with G-Rg3 increased HCV core protein-mediated reduction in the expression level of cytosolic p21, required for increasing cyclin-dependent kinase 1 activity, which catalyzes Ser616 phosphorylation of dynamin-related protein 1. The HCV-induced mitophagy, which follows mitochondrial fission, was also rescued by G-Rg3 treatment. CONCLUSION G-Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV-induced dynamin-related protein 1-mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection. (Hepatology 2017;66:758-771).
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Affiliation(s)
- Seong-Jun Kim
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea,Corresponding authors: Jae Young Jang, MD, PhD, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Yongsan-gu, Seoul 04401, South Korea, Phone: +82-2-7099863; Fax: +82-2-7099696; ; Seong-Jun Kim, PhD, Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea, Phone: +82-42-860-7477; Fax: +82-42-861-4246;
| | - Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul 04401, South Korea,Corresponding authors: Jae Young Jang, MD, PhD, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Yongsan-gu, Seoul 04401, South Korea, Phone: +82-2-7099863; Fax: +82-2-7099696; ; Seong-Jun Kim, PhD, Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea, Phone: +82-42-860-7477; Fax: +82-42-861-4246;
| | - Eun-Jung Kim
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea
| | - Eun Kyung Cho
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul 04401, South Korea
| | - Dae Gyun Ahn
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea
| | - Chonsaeng Kim
- Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, South Korea
| | - Han Seul Park
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul 04401, South Korea
| | - Soung Won Jeong
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul 04401, South Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan 31151, South Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon 14584, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon 14584, South Korea
| | - Hong Soo Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan 31151, South Korea
| | - Boo Sung Kim
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul 04401, South Korea
| | - Ji-Hyung Lee
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
| | - Aleem Siddiqui
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA,Division of Infectious Diseases, University of California, San Diego, La Jolla, CA 92093, USA
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Park HH, Choi SW, Lee GJ, Kim YD, Noh HJ, Oh SJ, Yoo I, Ha YJ, Koo GB, Hong SS, Kwon SW, Kim YS. A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death. J Ginseng Res 2017; 43:86-94. [PMID: 30662297 PMCID: PMC6323173 DOI: 10.1016/j.jgr.2017.08.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 08/09/2017] [Accepted: 08/14/2017] [Indexed: 01/01/2023] Open
Abstract
Background Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.
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Affiliation(s)
- Han-Hee Park
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Seung-Won Choi
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Gwang Jin Lee
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Young-Dae Kim
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hyun-Jin Noh
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Seung-Jae Oh
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Iseul Yoo
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Yu-Jin Ha
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Gi-Bang Koo
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
| | - Soon-Sun Hong
- College of Medicine, Inha University, Incheon, Republic of Korea
| | - Sung Won Kwon
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - You-Sun Kim
- Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea
- Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
- Corresponding author. Department of Biochemistry, Ajou University School of Medicine San 5, Wonchon-dong, Yeongtong-gu, Suwon 16499, Republic of Korea.
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Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property. Molecules 2017; 22:molecules22050844. [PMID: 28534845 PMCID: PMC6153937 DOI: 10.3390/molecules22050844] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 05/07/2017] [Accepted: 05/12/2017] [Indexed: 11/16/2022] Open
Abstract
Minor ginsenosides, such as compound K, Rg3(S), which can be produced by deglycosylation of ginsenosides Rb1, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb1, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b) derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231) in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb1. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries.
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