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Cui D, Zhang C, Zhang L, Zheng J, Wang J, He L, Jin H, Kang Q, Zhang Y, Li N, Sun Z, Zheng W, Wei J, Zhang S, Feng Y, Tan W, Zhong Z. Natural anti-cancer products: insights from herbal medicine. Chin Med 2025; 20:82. [PMID: 40490812 DOI: 10.1186/s13020-025-01124-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 05/05/2025] [Indexed: 06/11/2025] Open
Abstract
Herbal medicine exhibits a broad spectrum of potent anti-cancer properties, including the enhancement of tumor immune responses, reversal of multidrug resistance, regulation of autophagy and ferroptosis, as well as anti-proliferative, pro-apoptotic, and anti-metastatic effects. This review systematically explores recent advances (primarily documented since 2019) in research on key anti-cancer compounds derived from herbal medicine, such as apigenin, artemisinin, berberine, curcumin, emodin, epigallocatechin gallate (EGCG), ginsenosides, icariin, resveratrol, silibinin, triptolide, and ursolic acid (UA). These studies were sourced from scientific databases, including PubMed, Web of Science, Medline, Scopus, and Clinical Trials. The review focuses on the significant role that these natural products play in modern oncology, exploring their efficacy, mechanisms of action, and the challenges and prospects of integrating them into conventional cancer therapies. Furthermore, it highlights cutting-edge approaches in cancer research, such as the utilization of gut microbiota, omics technologies, synthetic derivatives, and advanced drug delivery systems (DDS). This review underscores the potential of these natural products to advance the development of novel anti-cancer treatments and support contemporary medicine. Additionally, recent multi-omics findings reveal how these compounds reshape transcriptional and metabolic networks, further broadening their therapeutic scope. Many natural products exhibit synergy with first-line chemotherapies or targeted therapies, thereby enhancing treatment efficacy and reducing side effects. Advanced nano-formulations and antibody-drug conjugates have also substantially improved their bioavailability, making them promising candidates for future translational research.
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Affiliation(s)
- Dianxin Cui
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Cheng Zhang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 6/F, 3 Sassoon Road, Pokfulam, Hong Kong S.A.R., 999077, China
| | - Lili Zhang
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Jingbin Zheng
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Jie Wang
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Luying He
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Haochun Jin
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Qianming Kang
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Yang Zhang
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Na Li
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Zhenlong Sun
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wenying Zheng
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Jinchao Wei
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Siyuan Zhang
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 6/F, 3 Sassoon Road, Pokfulam, Hong Kong S.A.R., 999077, China.
| | - Wen Tan
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China.
| | - Zhangfeng Zhong
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao S.A.R., 999078, China.
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Yan H, Wu X, Li H, Yu Z, Jin X. Pan-Cancer Analysis Identifies BCLAF1 as a Potential Biomarker for Renal Cell Carcinoma. Biochem Genet 2025; 63:1479-1508. [PMID: 38573525 DOI: 10.1007/s10528-024-10773-x] [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: 07/04/2023] [Accepted: 03/04/2024] [Indexed: 04/05/2024]
Abstract
B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) is a versatile protein involved in the regulation of gene transcription and post-transcriptional processing. Although BCLAF1 exerts a broad tumor suppressor effect or tumor promoter effect in many cancer types, the specific roles concerning its expression levels, and its impact on tumorigenesis in Renal cell carcinoma (RCC) remain unclear. Here, we utilized the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) datasets alongside R software and online tools to unravel the specific roles of BCLAF1 in 33 cancer types, including its expression levels, tumor immune and molecular subtypes, and its correlation with prognosis, diagnosis, DNA methylation, and immune microenvironment. Additionally, we carried out cell biology experiments to independently investigate the expression of BCLAF1 in RCC and its effects on tumor progression. BCLAF1 was differentially expressed in tumor tissues compared to normal tissues across various cancer types and was also differentially expressed in different immune and molecular subtypes. In RCC, patients with high BCLAF1 expression had a better prognosis and BCLAF1 was tightly correlated with the stage, gender, and histological grade of patients. Furthermore, BCLAF1 had higher DNA methylation levels and higher immune infiltration levels in tumor tissues. Additionally, cell functional experiments confirmed the low expression of BCLAF1 in RCC and that BCLAF1 significantly inhibited the proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest in RCC cells in vitro. Our study under-scored the potential of BCLAF1 as an important actor in tumorigenesis, especially concerning RCC where it may serve as an effective prognostic marker.
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Affiliation(s)
- Huan Yan
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xiang Wu
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China
| | - Hong Li
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China
| | - Zongdong Yu
- Department of Neurosurgery, Shangrao People's Hospital, Shangrao, 334099, China.
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China.
| | - Xiaofeng Jin
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, 315211, China.
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Shang S, Yang H, Qu L, Fan D, Deng J. Ginsenoside, a potential natural product against liver diseases: a comprehensive review from molecular mechanisms to application. Crit Rev Food Sci Nutr 2025:1-25. [PMID: 39810734 DOI: 10.1080/10408398.2025.2451761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Liver disease constitutes a significant cause of global mortality, with its pathogenesis being multifaceted. Identifying effective pharmacological and preventive strategies is imperative for liver protection. Ginsenosides, the major bioactive compounds found in ginseng, exhibit multiple pharmacological activities including protection against liver-related diseases by mitigating liver fat accumulation and inflammation, preventing hepatic fibrosis, and exerting anti-hepatocarcinogenic effects. However, a comprehensive overview elucidating the regulatory pathways associated with ginsenosides in liver disease remains elusive. This review aims to consolidate the molecular mechanisms through which different ginsenosides ameliorate distinct liver diseases, alongside the pathogenic factors underlying liver ailments. Notably, ginsenosides Rb1 and Rg1 demonstrate significantly effective in treating fatty liver, hepatitis, and liver fibrosis, and ginsenosides CK and Rh2 exhibit potent anti-hepatocellular carcinogenic effects. Their molecular mechanisms underlying these effects primarily involve the modulation of AMPK, NF-κB, TGF-β, NFR2, JNK, and other pathways, thereby attenuating hepatic fat accumulation, inflammation, inhibition of hepatic stellate cell activation, and promoting apoptosis in hepatocellular carcinoma cells. Furthermore, it provides insights into the safety profile and current applications of ginsenosides, thereby facilitating their clinical development. Consequently, ginsenosides present promising prospects for liver disease management, underscoring their potential as valuable therapeutic agents in this context.
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Affiliation(s)
- Shiyan Shang
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Haixia Yang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Linlin Qu
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Daidi Fan
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Jianjun Deng
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
- State Key Laboratory of Vegetable Biobreeding, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China
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Muhammad SNH, Ramli RR, Nik Mohamed Kamal NNS, Fauzi AN. Terpenoids: Unlocking Their Potential on Cancer Glucose Metabolism. Phytother Res 2024; 38:5626-5640. [PMID: 39300823 DOI: 10.1002/ptr.8346] [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: 06/25/2024] [Revised: 09/04/2024] [Accepted: 09/05/2024] [Indexed: 09/22/2024]
Abstract
Cancer incidence has increased globally and has become the leading cause of death in the majority of countries. Many cancers have altered energy metabolism pathways, such as increased glucose uptake and glycolysis, as well as decreased oxidative phosphorylation. This is known as the Warburg effect, where cancer cells become more reliant on glucose to generate energy and produce lactate as an end product, even when oxygen is present. These are attributed to the overexpression of key glycolytic enzymes, glucose transporters, and related signaling pathways that occur in cancer cells. Therefore, overcoming metabolic alterations in cancer cells has recently become a target for therapeutic approaches. Natural products have played a key role in drug discovery, especially for cancer and infectious diseases. In this review, we are going to focus on terpenoids, which are gradually gaining popularity among drug researchers due to their reported anti-cancer effects via cell cycle arrest, induction of apoptosis, reduction of proliferation, and metastasis. This review summarizes the potential of 13 terpenoid compounds as anti-glycolytic inhibitors in different cancer models, primarily by inhibiting the glucose uptake and the generation of lactate, as well as by downregulating enzymes associated to glycolysis. As a conclusion, disruption of cancer cell glycolysis may be responsible for the anti-cancer activity of terpenoids.
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Affiliation(s)
- Siti Nur Hasyila Muhammad
- Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Redzyque Ramza Ramli
- Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Nik Nur Syazni Nik Mohamed Kamal
- Department of Toxicology, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Pulau Pinang, Malaysia
| | - Agustine Nengsih Fauzi
- Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
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Chen J, Cheng H, Bai C, Wang D, Fu J, Hao J, Wang Y, Xuewu Z. Sorbaria sorbifolia flavonoid derivative induces mitochondrial apoptosis in human hepatoma cells through Bclaf1. Front Pharmacol 2024; 15:1459520. [PMID: 39444606 PMCID: PMC11496133 DOI: 10.3389/fphar.2024.1459520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 08/30/2024] [Indexed: 10/25/2024] Open
Abstract
4',5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine Sorbaria sorbifolia. 4',5-Dihydroxy-7-piperazinemethoxy-8-methoxy flavonoids (DMF) with good solubility and anti-tumor effects was obtained by chemical modification in the early stage. This study explored the mechanism by which DMF regulates the mitochondrial apoptosis of human hepatoma cells through Bcl-2-associated transcription factor 1 (Bclaf1). DMF inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner and induced cell mitochondrial apoptosis. The molecular docking and cell assay results demonstrated that DMF inhibits Bclaf1 expression by binding to its active site. Lentivirus transfection was used to construct cells with stable knockout and overexpression of Bclaf1, and a Hep3B xenograft model was constructed in nude mice. The mechanism by which DMF induced the mitochondrial apoptosis of human hepatoma cells through Bclaf1 was further verified in vitro and in vivo. These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1.
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Affiliation(s)
| | | | | | | | | | | | | | - Zhang Xuewu
- College of Medicine, Yanbian University, Yanji, China
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Zhou Y, Ran X, Han M. BCLAF1 is Expressed as a Potential Anti-oncogene in Bile Duct Cancer. Biochem Genet 2024; 62:3681-3694. [PMID: 38198022 DOI: 10.1007/s10528-023-10616-1] [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: 08/19/2023] [Accepted: 11/29/2023] [Indexed: 01/11/2024]
Abstract
Validating the role of BCLAF1 in the development of Bile Duct Cancer. Differential expression of BCLAF1 in Bile Duct Cancer and normal tissues was analyzed bioinformatically, and immuno-infiltration analysis was performed by R. We also derived the correlation between the expression of BCLAF1 and HIF-1α by bioinformatics analysis and validated it by Western Blotting, qRT-PCR and scratch assays before and after hypoxia. Through bioinformatics analysis, we found that BCLAF1 mRNA was significantly higher in the tumor tissues of Bile Duct Cancer. The high expression of BCLAF1 implied a more advanced stage but a lower mortality rate. KEGG and GO enrichment analysis showed that BCLAF1 overexpression in Bile Duct Cancer was mainly associated with histone modification, peptidyl lysine modification, and macromolecular methylation. We used the TIMER algorithm to show that BCLAF1 expression in Bile Duct Cancer is associated with immune cell infiltration, which affects tumor progression and patient prognosis. We confirmed by normoxia and hypoxia qRT-PCR, Western Blotting and scratch assays that BCLAF1 and HIF-1α expression are positively correlated and that BCLAF1 may be expressed as anti-oncogene in Bile Duct Cancer. These findings demonstrate that BCLAF1 may act as anti-oncogene in Bile Duct Cancer and may be involved in immune cell infiltration in Bile Duct Cancer, suppressing the expression of HIF-1α.
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Affiliation(s)
- Yutong Zhou
- Department of Postgraduates, Guizhou Medical University, Guizhou, China
| | - Xun Ran
- Affiliated Hospital of Guizhou Medical University, Guizhou, China
| | - Min Han
- Affiliated Hospital of Guizhou Medical University, Guizhou, China.
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guizhou Medical University, Beijing Road, Guiyang, 550000, Guizhou Province, 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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Jian HY, Liang ZC, Wen H, Zhang Z, Zeng PH. Shi-pi-xiao-ji formula suppresses hepatocellular carcinoma by reducing cellular stiffness through upregulation of acetyl-coA acetyltransferase 1. World J Gastrointest Oncol 2024; 16:2727-2741. [PMID: 38994152 PMCID: PMC11236261 DOI: 10.4251/wjgo.v16.i6.2727] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 03/14/2024] [Accepted: 04/23/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji (SPXJ) herbal decoction formula is effective in suppressing hepatocellular carcinoma (HCC), but the underlying mechanisms are not known. Therefore, this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1 (ACAT1)-regulated cellular stiffness. Through a series of experiments, we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1, lowering the level of cholesterol in the cell membrane, and altering the cellular stiffness, which provides a new idea for the research of traditional Chinese medicine against HCC. AIM To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC. METHODS HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice. The apoptotic rate and proliferative, invasive, and migratory abilities of control and SPXJ-treated HCC cells were compared. Atomic force microscopy was used to determine the cell surface morphology and the Young's modulus values of the control and SPXJ-treated HCC cells. Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit. ACAT1 protein levels were estimated using western blotting. RESULTS Compared with the vehicle group, SPXJ serum considerably reduced proliferation of HCC cells, increased stiffness and apoptosis of HCC cells, inhibited migration and invasion of HCC cells, decreased plasma membrane cholesterol levels, and upregulated ACAT1 protein levels. However, treatment of HCC cells with the water-soluble cholesterol promoted proliferation, migration, and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels, but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control. CONCLUSION SPXJ formula inhibited proliferation, invasion, and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression.
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Affiliation(s)
- Hui-Ying Jian
- Graduate School, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Zi-Cheng Liang
- Graduate School, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Huan Wen
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha 410006, Hunan Province, China
| | - Zhen Zhang
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha 410006, Hunan Province, China
| | - Pu-Hua Zeng
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha 410006, Hunan Province, China
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Jian HY, Liang ZC, Wen H, Zhang Z, Zeng PH. Shi-pi-xiao-ji formula suppresses hepatocellular carcinoma by reducing cellular stiffness through upregulation of acetyl-coA acetyltransferase 1. World J Gastrointest Oncol 2024; 16:2715-2729. [DOI: 10.4251/wjgo.v16.i6.2715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 03/14/2024] [Accepted: 04/23/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji (SPXJ) herbal decoction formula is effective in suppressing hepatocellular carcinoma (HCC), but the underlying mechanisms are not known. Therefore, this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1 (ACAT1)-regulated cellular stiffness. Through a series of experiments, we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1, lowering the level of cholesterol in the cell membrane, and altering the cellular stiffness, which provides a new idea for the research of traditional Chinese medicine against HCC.
AIM To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC.
METHODS HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice. The apoptotic rate and proliferative, invasive, and migratory abilities of control and SPXJ-treated HCC cells were compared. Atomic force microscopy was used to determine the cell surface morphology and the Young’s modulus values of the control and SPXJ-treated HCC cells. Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit. ACAT1 protein levels were estimated using western blotting.
RESULTS Compared with the vehicle group, SPXJ serum considerably reduced proliferation of HCC cells, increased stiffness and apoptosis of HCC cells, inhibited migration and invasion of HCC cells, decreased plasma membrane cholesterol levels, and upregulated ACAT1 protein levels. However, treatment of HCC cells with the water-soluble cholesterol promoted proliferation, migration, and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels, but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control.
CONCLUSION SPXJ formula inhibited proliferation, invasion, and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression.
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Affiliation(s)
- Hui-Ying Jian
- Graduate School, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Zi-Cheng Liang
- Graduate School, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Huan Wen
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha 410006, Hunan Province, China
| | - Zhen Zhang
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha 410006, Hunan Province, China
| | - Pu-Hua Zeng
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha 410006, Hunan Province, China
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10
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Guo J, Yan W, Duan H, Wang D, Zhou Y, Feng D, Zheng Y, Zhou S, Liu G, Qin X. Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms. Nutrients 2024; 16:1642. [PMID: 38892575 PMCID: PMC11174683 DOI: 10.3390/nu16111642] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
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Affiliation(s)
- Jinhong Guo
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Wenjie Yan
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Hao Duan
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Diandian Wang
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Yaxi Zhou
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Duo Feng
- Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China;
| | - Yue Zheng
- College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China;
| | - Shiqi Zhou
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Gaigai Liu
- Beijing Key Laboratory of Bioactive Substances and Functional Food, Beijing Union University, Beijing 100023, China; (J.G.); (W.Y.); (H.D.); (D.W.); (Y.Z.); (S.Z.); (G.L.)
| | - Xia Qin
- Graduate Department, Beijing Union University, Beijing 100101, China
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11
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Chen J, Wang Z, Fu J, Cai Y, Cheng H, Cui X, Sun M, Liu M, Zhang X. Ginsenoside compound K induces ferroptosis via the FOXO pathway in liver cancer cells. BMC Complement Med Ther 2024; 24:174. [PMID: 38664638 PMCID: PMC11044296 DOI: 10.1186/s12906-024-04471-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Liver cancer is a common malignant tumor worldwide, traditional Chinese medicine is one of the treatment measures for liver cancer because of its good anti-tumor effects and fewer toxic side effects. Ginsenoside CK (CK) is an active component of ginseng. This study explored the mechanism by which CK induced ferroptosis in liver cancer cells. We found that CK inhibited the proliferation of HepG2 and SK-Hep-1 cells, induced ferroptosis of cells. Ferrostatin-1, an ferroptosis inhibitor, was used to verify the role of CK in inducing ferroptosis of liver cancer cells. Network pharmacological analysis identified the FOXO pathway as a potential mechanism of CK, and western blot showed that CK inhibited p-FOXO1. In cells treated with the FOXO1 inhibitor AS1842856, further verify the involvement of the FOXO pathway in regulating CK-induced ferroptosis in HepG2 and SK-Hep-1 cells. A HepG2 cell-transplanted tumor model was established in nude mice, and CK inhibited the growth of transplanted tumors in nude mice, p-FOXO1 was decreased in tumor tissues, and SLC7A11 and GPX4 expressions were also down-regulated after CK treatment. These findings suggested that CK induces ferroptosis in liver cancer cells by inhibiting FOXO1 phosphorylation and activating the FOXO signaling pathway, thus playing an antitumor role.
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Affiliation(s)
- Jiaxin Chen
- College of Medicine, Yanbian University, Yanji, China
| | - Zhuoshi Wang
- College of Medicine, Yanbian University, Yanji, China
| | - Jinghao Fu
- College of Medicine, Yanbian University, Yanji, China
| | - Yuesong Cai
- College of Medicine, Yanbian University, Yanji, China
| | - Haoyi Cheng
- College of Medicine, Yanbian University, Yanji, China
| | - Xinmu Cui
- College of Medicine, Yanbian University, Yanji, China
| | - Manqing Sun
- College of Medicine, Yanbian University, Yanji, China
| | - Mingyue Liu
- College of Medicine, Yanbian University, Yanji, China
| | - Xuewu Zhang
- College of Medicine, Yanbian University, Yanji, China.
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12
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Yu Z, Wu X, Zhu J, Yan H, Li Y, Zhang H, Zhong Y, Lin M, Ye G, Li X, Jin J, Li K, Wang J, Zhuang H, Lin T, He J, Lu C, Xu Z, Zhang X, Li H, Jin X. BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma. Cell Mol Life Sci 2024; 81:82. [PMID: 38340178 PMCID: PMC10858942 DOI: 10.1007/s00018-024-05144-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 12/21/2023] [Accepted: 01/23/2024] [Indexed: 02/12/2024]
Abstract
Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.
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Affiliation(s)
- Zongdong Yu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Xiang Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Jie Zhu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
| | - Huan Yan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
| | - Yuxuan Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Hui Zhang
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Yeling Zhong
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Man Lin
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Ganghui Ye
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Xinming Li
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Jiabei Jin
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Kailang Li
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Jie Wang
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Hui Zhuang
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Ting Lin
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Jian He
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China
| | - Changjiang Lu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
| | - Zeping Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
| | - Xie Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China
| | - Hong Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China.
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China.
| | - Xiaofeng Jin
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315040, China.
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Nngbo University, Ningbo, 315211, China.
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13
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Wang L, Shao L, Huang STZ, Liu Z, Zhang W, Hu K, Huang WH. Metabolic characteristics of ginsenosides from Panax ginseng in rat feces mediated by gut microbiota. J Pharm Biomed Anal 2024; 237:115786. [PMID: 37837893 DOI: 10.1016/j.jpba.2023.115786] [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: 08/09/2023] [Revised: 09/21/2023] [Accepted: 10/09/2023] [Indexed: 10/16/2023]
Abstract
Ginsenosides in Panax ginseng are regarded to be functional ingredients for diverse pharmacological effects and orally administrated with very low absorption in the gastrointestinal tract to be metabolized by gut microbiota. However, in vivo metabolic characteristics of ginsenosides mediated by gut microbiota are not well-known. This study aimed to explore the metabolic profiles of ginsenosides in rat feces mediated by gut microbiota. Ginsenosides and metabolites were identified and relatively quantified by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). As a result, eighty-four metabolites were identified in the normal control rat feces, while only thirty intermediates were found with very low yields in the pseudo-germ-free (GF) group. Similarly, the main bioconversion pathways of ginsenosides in vivo were the same deglycosylation reaction mediated by gut microbiota in vitro. The findings demonstrated significant differences in metabolic profiles between the normal control and pseudo-GF rats, which implied gut microbiota played an important role in the metabolism of ginsenosides.
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Affiliation(s)
- Lin Wang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China
| | - Li Shao
- Department of Pharmacognosy, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410128, China
| | - Su-Tian-Zi Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China
| | - Zhi Liu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Wei Zhang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China
| | - Kai Hu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Wei-Hua Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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14
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Yang C, Qian C, Zheng W, Dong G, Zhang S, Wang F, Wei Z, Xu Y, Wang A, Zhao Y, Lu Y. Ginsenoside Rh2 enhances immune surveillance of natural killer (NK) cells via inhibition of ERp5 in breast cancer. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155180. [PMID: 38043385 DOI: 10.1016/j.phymed.2023.155180] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 10/02/2023] [Accepted: 10/31/2023] [Indexed: 12/05/2023]
Abstract
BACKGROUND One critical component of the immune system that prevents breast cancer cells from forming distant metastasis is natural killer (NK) cells participating in immune responses to tumors. Ginsenoside Rh2 (GRh2) as one of the major active ingredients of ginseng has been employed in treatment of cancers, but the function of GRh2 in modulating the development of breast cancer remains elusive. PURPOSE This study was to dissect the effect of GRh2 against breast cancer and its potential mechanisms associated with NK cells, both in vitro and in vivo. METHODS MDA-MB-231 and 4T1 cells were used to establish in situ and hematogenous mouse models. MDA-MB-231 and MCF-7 were respectively co-cultured with NK92MI cells or primary NK cells in vitro. Anti-tumor efficacy of GRh2 was verified by immunohistochemistry (IHC), Cell Counting Kit-8 (CCK8), high resolution micro-computed tomography (micro-CT) scanning of lungs and hematoxylin and eosin (H&E) staining. Lactate dehydrogenase (LDH) cytotoxicity assay, flow cytometry, in vivo depletion of NK cells, enzyme-linked immunosorbent assay (ELISA), western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence and cell transfection were performed for investigating the anti-tumor mechanisms of GRh2. Molecular docking, microscale thermophoresis (MST) and cellular thermal shift assay (CETSA) were employed to determine the binding between endoplasmic reticulum protein 5 (ERp5) and GRh2. RESULTS We demonstrated that GRh2 exerted prominent impacts on retarding the growth and metastasis of breast cancer through boosting the cytotoxic function of NK cells, as validated by the elevated release of perforin, granzyme B and interferon-γ (IFN-γ). Mechanistical studies revealed that GRh2 was capable of diminishing the expression of ERp5 and GRh2 directly bound to ERp5 in MDA-MB-231 cells as well as on a recombinant protein level. GRh2 prevented the formation of soluble MICA (sMICA) and upregulated the expression level of MICA in vivo and in vitro. Importantly, the reduced lung metastasis of breast cancer by GRh2 was almost abolished upon the depletion of NK cells. Moreover, GRh2 was able to insert into the binding pocket of ERp5 directly. CONCLUSION We firstly demonstrated that GRh2 played a pivotal role in augmenting NK cell activity by virtue of modulating the NKG2D-MICA signaling axis via directly binding to ERp5, and may be further optimized to a therapeutic agent for the treatment of breast cancer.
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Affiliation(s)
- Chunmei Yang
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Cheng Qian
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Weiwei Zheng
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Guanglu Dong
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Shan Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Feihui Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Zhonghong Wei
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yuhua Xu
- Jiangsu Health Vocational College, Nanjing 211800, China
| | - Aiyun Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Yang Zhao
- Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Yin Lu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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15
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Liu C, Li S, Zhang C, Jin CH. Recent Advances in Research on Active Compounds Against Hepatic Fibrosis. Curr Med Chem 2024; 31:2571-2628. [PMID: 37497688 DOI: 10.2174/0929867331666230727102016] [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: 12/16/2022] [Revised: 05/14/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND Almost all chronic liver diseases cause fibrosis, which can lead to cirrhosis and eventually liver cancer. Liver fibrosis is now considered to be a reversible pathophysiological process and suppression of fibrosis is necessary to prevent liver cancer. At present, no specific drugs have been found that have hepatic anti-fibrotic activity. OBJECTIVE The research progress of anti-hepatic fibrosis compounds in recent ten years was reviewed to provide a reference for the design and development of anti-hepatic fibrosis drugs. METHODS According to the structure of the compounds, they are divided into monocyclic compounds, fused-heterocyclic compounds, and acyclic compounds. RESULTS In this article, the natural products and synthetic compounds with anti-fibrotic activity in recent ten years were reviewed, with emphasis on their pharmacological activity and structure-activity relationship (SAR). CONCLUSION Most of these compounds are natural active products and their derivatives, and there are few researches on synthetic compounds and SAR studies on natural product.
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Affiliation(s)
- Chuang Liu
- Key Laboratory of Natural Resources of Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China
| | - Siqi Li
- Key Laboratory of Natural Resources of Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China
| | - Changhao Zhang
- Key Laboratory of Natural Resources of Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China
| | - Cheng-Hua Jin
- Key Laboratory of Natural Resources of Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China
- Interdisciplinary of Biological Functional Molecules, College of Integration Science, Yanbian University, Yanji, Jilin, 133002, China
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16
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Yao B, Lu Y, Li Y, Bai Y, Wei X, Yang Y, Yao D. BCLAF1-induced HIF-1α accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex. Cancer Immunol Immunother 2023; 72:4279-4292. [PMID: 37906282 PMCID: PMC10700218 DOI: 10.1007/s00262-023-03563-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 10/17/2023] [Indexed: 11/02/2023]
Abstract
Bcl-2-associated transcription factor-1 (BCLAF1), an apoptosis-regulating protein of paramount significance, orchestrates the progression of various malignancies. This study reveals increased BCLAF1 expression in hepatocellular carcinoma (HCC) patients, in whom elevated BCLAF1 levels are linked to escalated tumor grades and diminished survival rates. Moreover, novel BCLAF1 expression is particularly increased in HCC patients who were not sensitive to the combined treatment of atezolizumab and bevacizumab, but not in patients who had tumors that responded to the combined regimen. Notably, overexpression of BCLAF1 increases HCC cell proliferation in vitro and in vivo, while the conditioned medium derived from cells overexpressing BCLAF1 strikingly enhances the tube-formation capacity of human umbilical vein endothelial cells. Furthermore, compelling evidence demonstrates that BCLAF1 attenuates the expression of prolyl hydroxylase domain protein 2 (PHD2) and governs the stability of hypoxia-inducible factor-1α (HIF-1α) under normoxic conditions without exerting any influence on transcription, as determined by Western blot and RT‒qPCR analyses. Subsequently, employing coimmunoprecipitation and immunofluorescence, we validated the reciprocal interaction between BCLAF1 and Cullin 3 (CUL3), through which BCLAF1 actively upregulates the ubiquitination and degradation of PHD2. The Western blot and RT‒qPCR results suggests that programmed death ligand-1 (PD-L1) is one of the downstream responders to HIF-1α in HCC. Thus, we reveal the pivotal role of BCLAF1 in promoting PD-L1 transcription and, through binding to CUL3, in promoting the accumulation of HIF-1α under normoxic conditions, thereby facilitating the ubiquitination and degradation of PHD2.
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Affiliation(s)
- Bowen Yao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ye Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yazhao Li
- Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yixue Bai
- Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Xinyu Wei
- Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Yuanyuan Yang
- Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Demao Yao
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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17
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Shuvalov O, Kirdeeva Y, Daks A, Fedorova O, Parfenyev S, Simon HU, Barlev NA. Phytochemicals Target Multiple Metabolic Pathways in Cancer. Antioxidants (Basel) 2023; 12:2012. [PMID: 38001865 PMCID: PMC10669507 DOI: 10.3390/antiox12112012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 11/09/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
Cancer metabolic reprogramming is a complex process that provides malignant cells with selective advantages to grow and propagate in the hostile environment created by the immune surveillance of the human organism. This process underpins cancer proliferation, invasion, antioxidant defense, and resistance to anticancer immunity and therapeutics. Perhaps not surprisingly, metabolic rewiring is considered to be one of the "Hallmarks of cancer". Notably, this process often comprises various complementary and overlapping pathways. Today, it is well known that highly selective inhibition of only one of the pathways in a tumor cell often leads to a limited response and, subsequently, to the emergence of resistance. Therefore, to increase the overall effectiveness of antitumor drugs, it is advisable to use multitarget agents that can simultaneously suppress several key processes in the tumor cell. This review is focused on a group of plant-derived natural compounds that simultaneously target different pathways of cancer-associated metabolism, including aerobic glycolysis, respiration, glutaminolysis, one-carbon metabolism, de novo lipogenesis, and β-oxidation of fatty acids. We discuss only those compounds that display inhibitory activity against several metabolic pathways as well as a number of important signaling pathways in cancer. Information about their pharmacokinetics in animals and humans is also presented. Taken together, a number of known plant-derived compounds may target multiple metabolic and signaling pathways in various malignancies, something that bears great potential for the further improvement of antineoplastic therapy.
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Affiliation(s)
- Oleg Shuvalov
- Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia; (Y.K.); (A.D.); (O.F.)
| | - Yulia Kirdeeva
- Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia; (Y.K.); (A.D.); (O.F.)
| | - Alexandra Daks
- Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia; (Y.K.); (A.D.); (O.F.)
| | - Olga Fedorova
- Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia; (Y.K.); (A.D.); (O.F.)
| | - Sergey Parfenyev
- Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia; (Y.K.); (A.D.); (O.F.)
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland;
- Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia
| | - Nickolai A. Barlev
- Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia; (Y.K.); (A.D.); (O.F.)
- Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia
- Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana 20000, Kazakhstan
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18
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Yu S, Zhao R, Zhang B, Lai C, Li L, Shen J, Tan X, Shao J. Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma. Asian J Pharm Sci 2023; 18:100828. [PMID: 37583709 PMCID: PMC10424087 DOI: 10.1016/j.ajps.2023.100828] [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: 12/07/2022] [Revised: 04/17/2023] [Accepted: 07/10/2023] [Indexed: 08/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is now a common cause of cancer death, with no obvious change in patient survival over the past few years. Although the traditional therapeutic modalities for HCC patients mainly involved in surgery, chemotherapy, and radiotherapy, which have achieved admirable achievements, challenges are still existed, such as drug resistance and toxicity. The emerging gene therapy of clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9-based (CRISPR/Cas9), as an alternative to traditional treatment methods, has attracted considerable attention for eradicating resistant malignant tumors and regulating multiple crucial events of target gene-editing. Recently, advances in CRISPR/Cas9-based anti-drugs are presented at the intersection of science, such as chemistry, materials science, tumor biology, and genetics. In this review, the principle as well as statues of CRISPR/Cas9 technique were introduced first to show its feasibility. Additionally, the emphasis was placed on the applications of CRISPR/Cas9 technology in therapeutic HCC. Further, a broad overview of non-viral delivery systems for the CRISPR/Cas9-based anti-drugs in HCC treatment was summarized to delineate their design, action mechanisms, and anticancer applications. Finally, the limitations and prospects of current studies were also discussed, and we hope to provide comprehensively theoretical basis for the designing of anti-drugs.
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Affiliation(s)
- Shijing Yu
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Ruirui Zhao
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Bingchen Zhang
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Chunmei Lai
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Linyan Li
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Jiangwen Shen
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Xiarong Tan
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
| | - Jingwei Shao
- Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
- College of Materials and Chemical Engineering, Minjiang University, Fuzhou 350108, China
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19
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Huang Y, Ran X, Liu H, Luo M, Qin Y, Yan J, Li X, Jia Y. A novel dammarane triterpenoid alleviates atherosclerosis by activating the LXRα pathway. Chin Med 2023; 18:72. [PMID: 37322486 DOI: 10.1186/s13020-023-00758-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 04/24/2023] [Indexed: 06/17/2023] Open
Abstract
BACKGROUND We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it. METHODS Male C57BL/6 ApoE-/- mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα. RESULTS After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE-/- mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation. CONCLUSIONS Our results revealed that CKN prevented the formation of atherosclerosis in ApoE-/- mice by activating the LXRα pathway.
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Affiliation(s)
- Yan Huang
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China
| | - Xiaodong Ran
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China
| | - Hongmei Liu
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China
| | - Mingming Luo
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China
| | - Yiyu Qin
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China
| | - Jinqiong Yan
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China
| | - Xiaohui Li
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China.
| | - Yi Jia
- Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing, 400038, China.
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20
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Tang M, Deng H, Zheng K, He J, Yang J, Li Y. Ginsenoside 3β-O-Glc-DM (C3DM) suppressed glioma tumor growth by downregulating the EGFR/PI3K/AKT/mTOR signaling pathway and modulating the tumor microenvironment. Toxicol Appl Pharmacol 2023; 460:116378. [PMID: 36641037 DOI: 10.1016/j.taap.2023.116378] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 12/18/2022] [Accepted: 01/09/2023] [Indexed: 01/13/2023]
Abstract
Ginsenosides are the main bioactive constituents of Panax ginseng, which have been broadly studied in cancer treatment. Our previous studies have demonstrated that 3β-O-Glc-DM (C3DM), a biosynthetic ginsenoside, exhibited antitumor effects in several cancer cell lines with anti-colon cancer activity superior to ginsenoside 20(R)-Rg3 in vivo. However, the efficacy of C3DM on glioma has not been proved yet. In this study, the antitumor activities and underlying mechanisms of C3DM on glioma were investigated in vitro and in vivo. Cell viability, apoptosis, migration, FCM, IHC, RT-qPCR, quantitative proteomics, and western blotting were conducted to evaluate the effect of C3DM on glioma cells. ADP-Glo™ kinase assay was used to validate the interaction between C3DM and EGFR. Co-cultured assays, lactic acid kit, and spatially resolved metabolomics were performed to study the function of C3DM in regulating glioma microenvironment. Both subcutaneously transplanted syngeneic models and orthotopic models of glioma were used to determine the effect of C3DM on tumor growth in vivo. We found that C3DM dose-dependently induced apoptosis, and inhibited the proliferation, migration and angiogenesis of glioma cells. C3DM significantly inhibited tumor growth in both subcutaneous and orthotopic mouse glioma models. Moreover, C3DM attenuated the acidified glioma microenvironment and enhanced T-cell function. Additionally, C3DM inhibited the kinase activity of EGFR and influenced the EGFR/PI3K/AKT/mTOR signaling pathway in glioma. Overall, C3DM might be a promising candidate for glioma prevention and treatment.
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Affiliation(s)
- Mei Tang
- Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Haidong Deng
- Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Kailu Zheng
- Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jiuming He
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jinling Yang
- NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yan Li
- Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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21
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Zhao Z, Su J, Zhao J, Chen J, Cui X, Sun M, Zhang X. Curcumin inhibits invasion and metastasis of human hepatoma cells through Bclaf1-mediated Wnt/β-catenin signalling. FOOD AGR IMMUNOL 2022. [DOI: 10.1080/09540105.2022.2113864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Zhongwei Zhao
- Medical College, Yanbian University, Yanji, People’s Republic of China
- College of Special Education, Changchun University, Changchun, People’s Republic of China
| | - Jielin Su
- Medical College, Yanbian University, Yanji, People’s Republic of China
| | - Jiaqi Zhao
- Medical College, Yanbian University, Yanji, People’s Republic of China
| | - Jiaxin Chen
- Medical College, Yanbian University, Yanji, People’s Republic of China
| | - Xinmu Cui
- Medical College, Yanbian University, Yanji, People’s Republic of China
| | - Manqing Sun
- Medical College, Yanbian University, Yanji, People’s Republic of China
| | - Xuewu Zhang
- Medical College, Yanbian University, Yanji, People’s Republic of China
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22
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Chen J, Sun M, Cui X, Zhang X. Ginsenoside compound K induces mitochondrial apoptosis in human hepatoma cells through Bclaf1-mediated modulation of ERK signaling. FOOD AGR IMMUNOL 2022. [DOI: 10.1080/09540105.2022.2134313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Jiaxin Chen
- College of Medicine, Yanbian University, Yanji, People’s Republic of China
| | - Manqing Sun
- College of Medicine, Yanbian University, Yanji, People’s Republic of China
| | - Xinmu Cui
- College of Medicine, Yanbian University, Yanji, People’s Republic of China
| | - Xuewu Zhang
- College of Medicine, Yanbian University, Yanji, People’s Republic of China
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23
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Ginsenosides in cancer: A focus on the regulation of cell metabolism. Biomed Pharmacother 2022; 156:113756. [DOI: 10.1016/j.biopha.2022.113756] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/17/2022] [Accepted: 09/26/2022] [Indexed: 11/23/2022] Open
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24
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Tang D, Zhao L, Mu R, Ao Y, Zhang X, Li X. LncRNA colorectal neoplasia differentially expressed promotes glycolysis of liver cancer cells by regulating hypoxia-inducible factor 1α. CHINESE J PHYSIOL 2022; 65:311-318. [PMID: 36588357 DOI: 10.4103/0304-4920.365458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
LncRNAs are associated with tumorigenesis of liver cancer. LncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) was identified as an oncogenic lncRNA and involved in tumor growth and metastasis. The role of CRNDE in liver cancer was investigated. CRNDE was elevated in liver cancer cells. Knockdown of CRNDE decreased cell viability and inhibited proliferation of liver cancer. Moreover, knockdown of CRNDE reduced levels of extracellular acidification rate, glucose consumption, and lactate production to repress glycolysis of liver cancer. Silence of CRNDE enhanced the expression of miR-142 and reduced enhancer of zeste homolog 2 (EZH2) and hypoxia-inducible factor 1α (HIF-1α). Over-expression of HIF-1α attenuated CRNDE silence-induced decrease of glucose consumption and lactate production. Injection with sh-CRNDE virus reduced in vivo tumor growth of liver cancer through up-regulation of miR-142 and down-regulation of EZH2 and HIF-1α. In conclusion, knockdown of CRNDE suppressed cell proliferation, glycolysis, and tumor growth of liver cancer through EZH2/miR-142/HIF-1α.
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Affiliation(s)
- Dan Tang
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Lijin Zhao
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Rui Mu
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Yu Ao
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Xuyang Zhang
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Xiongxiong Li
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
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25
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Ni B, Song X, Shi B, Wang J, Sun Q, Wang X, Xu M, Cao L, Zhu G, Li J. Research progress of ginseng in the treatment of gastrointestinal cancers. Front Pharmacol 2022; 13:1036498. [PMID: 36313365 PMCID: PMC9603756 DOI: 10.3389/fphar.2022.1036498] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 10/03/2022] [Indexed: 11/24/2022] Open
Abstract
Cancer has become one of the major causes of human death. Several anticancer drugs are available; howeve their use and efficacy are limited by the toxic side effects and drug resistance caused by their continuous application. Many natural products have antitumor effects with low toxicity and fewer adverse effects. Moreover, they play an important role in enhancing the cytotoxicity of chemotherapeutic agents, reducing toxic side effects, and reversing chemoresistance. Consequently, natural drugs are being applied as potential therapeutic options in the field of antitumor treatment. As natural medicinal plants, some components of ginseng have been shown to have excellent efficacy and a good safety profile for cancer treatment. The pharmacological activities and possible mechanisms of action of ginseng have been identified. Its broad range of pharmacological activities includes antitumor, antibacterial, anti-inflammatory, antioxidant, anti-stress, anti-fibrotic, central nervous system modulating, cardioprotective, and immune-enhancing effects. Numerous studies have also shown that throuth multiple pathways, ginseng and its active ingredients exert antitumor effects on gastrointestinal (GI) tract tumors, such as esophageal, gastric, colorectal, liver, and pancreatic cancers. Herein, we introduced the main components of ginseng, including ginsenosides, polysaccharides, and sterols, etc., and reviewed the mechanism of action and research progress of ginseng in the treatment of various GI tumors. Futhermore, the pathways of action of the main components of ginseng are discussed in depth to promote the clinical development and application of ginseng in the field of anti-GI tumors.
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Affiliation(s)
- Baoyi Ni
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaotong Song
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bolun Shi
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jia Wang
- Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China
| | - Qianhui Sun
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinmiao Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Manman Xu
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Luchang Cao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | | | - Jie Li
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Jie Li,
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26
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Bai C, Zhao J, Su J, Chen J, Cui X, Sun M, Zhang X. Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1-mediated modulation of PI3K/AKT/GSK-3β signaling. Life Sci 2022; 306:120804. [PMID: 35882275 DOI: 10.1016/j.lfs.2022.120804] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/01/2022] [Accepted: 07/10/2022] [Indexed: 12/28/2022]
Abstract
Curcumin is a yellow pigment extracted from the rhizome of turmeric, a traditional Chinese medicine. Here, we tested the hypothesis that curcumin-mediated downregulation of BCLAF1 triggers mitochondrial apoptosis in hepatoma cells by inhibiting PI3K/AKT/GSK-3β signaling. Treatment of the human hepatoma cell lines, HepG2 and SK-Hep-1, with various concentrations of curcumin revealed a time-dependent and concentration-dependent inhibition of cell proliferation, increased apoptosis, cell cycle arrest at the G0/G1 phase, reduced mitochondrial membrane potential, and reduced expression levels of PI3K, p-PI3K, AKT, p-AKT, GSK-3β, and p-GSK-3β. Additionally, curcumin suppressed the levels of apoptotic factors after treating the cells with LY294002, a PI3K inhibitor. Curcumin also suppressed the expression of BCLAF1. Treating stable BCLAF1 knockout HepG2 and SK-Hep-1 cells with curcumin further enhanced apoptosis and increased the number of cells in G0/G1 cell cycle arrest, while inhibiting the downregulation of PI3K/AKT/GSK-3β pathway-related proteins. Treatment of a nude mouse xenograft model bearing HepG2 cells with curcumin inhibited tumor growth, disrupted the cellular structure of the tumor tissue, and suppressed the expression of BCLAF1 and PI3K/AKT/GSK-3β proteins. In summary, our in vitro and in vivo analyses show that curcumin downregulates BCLAF1 expression, inhibits the activation of the PI3K/AKT/GSK-3β pathway, and triggers mitochondrial apoptosis in HCC. These findings uncover a potential therapeutic strategy leveraging the antitumor effects of curcumin against HCC.
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Affiliation(s)
- Chunhua Bai
- Yanbian University School of Medicine, Yanji 133000, China; Shenzhen Hyzen Hospital, Shenzhen 518000, China
| | - Jiaqi Zhao
- Yanbian University School of Medicine, Yanji 133000, China
| | - Jielin Su
- Yanbian University School of Medicine, Yanji 133000, China
| | - Jiaxin Chen
- Yanbian University School of Medicine, Yanji 133000, China
| | - Xinmu Cui
- Yanbian University School of Medicine, Yanji 133000, China
| | - Manqing Sun
- Yanbian University School of Medicine, Yanji 133000, China
| | - Xuewu Zhang
- Yanbian University School of Medicine, Yanji 133000, China.
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27
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Yu Z, Zhu J, Wang H, Li H, Jin X. Function of BCLAF1 in human disease. Oncol Lett 2022; 23:58. [PMID: 34992690 PMCID: PMC8721854 DOI: 10.3892/ol.2021.13176] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 09/22/2021] [Indexed: 02/06/2023] Open
Abstract
Originally identified as a regulator of apoptosis and transcription, B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) has since been shown to be associated with a multitude of biological processes, such as DNA damage response, splicing and processing of pre-mRNA, T-cell activation, lung development, muscle cell proliferation and differentiation, autophagy, ischemia-reperfusion injury, and viral infection. In recent years, an increasing amount of evidence has shown that BCLAF1 acts as either a tumor promoter or tumor suppressor in tumorigenesis depending on the cellular context and the type of cancer. Even in the same tumor type, BCLAF1 may have opposite effects. In the present review, the subcellular localization, structural features, mutations within BCLAF1 will be described, then the regulation of BCLAF1 and its downstream targets will be analyzed. Furthermore, the different roles and possible mechanisms of BCLAF1 in tumorigenesis will also be highlighted and discussed. Finally, BCLAF1 may be considered as a potential target for cancer therapy in the future.
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Affiliation(s)
- Zongdong Yu
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center of LiHuiLi Hospital, Ningbo University, Ningbo, Zhejiang 315040, P.R. China.,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Jie Zhu
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center of LiHuiLi Hospital, Ningbo University, Ningbo, Zhejiang 315040, P.R. China.,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Haibiao Wang
- Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Hong Li
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center of LiHuiLi Hospital, Ningbo University, Ningbo, Zhejiang 315040, P.R. China.,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - Xiaofeng Jin
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center of LiHuiLi Hospital, Ningbo University, Ningbo, Zhejiang 315040, P.R. China.,Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China
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28
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Zhang Y, Qiu Z, Zhu M, Teng Y. Ginsenoside Compound K Assisted G-Quadruplex Folding and Regulated G-Quadruplex-Containing Transcription. Molecules 2021; 26:molecules26237339. [PMID: 34885920 PMCID: PMC8659241 DOI: 10.3390/molecules26237339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/23/2021] [Accepted: 11/30/2021] [Indexed: 11/20/2022] Open
Abstract
Ginsenoside compound K (CK) is one of the major metabolites of the bioactive ingredients in Panax ginseng, which presents excellent bioactivity and regulates the expression of important proteins. In this work, the effects of CK on G-quadruplexes (G4s) were quantitatively analyzed in the presence and absence of their complementary sequences. CK was demonstrated to facilitate the formation of G4s, and increase the quantity of G4s in the competition with duplex. Thermodynamic experiments suggested that the electrostatic interactions were important for G4 stabilization by CK. CK was further found to regulate the transcription of G4-containing templates, reduce full-length transcripts, and decrease the transcription efficiency. Our results provide new evidence for the pharmacological study of ginsenosides at the gene level.
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Affiliation(s)
| | | | | | - Ye Teng
- Correspondence: ; Tel.: +86-13843132210
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29
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Zhou L, Li ZK, Li CY, Liang YQ, Yang F. Anticancer properties and pharmaceutical applications of ginsenoside compound K: A review. Chem Biol Drug Des 2021; 99:286-300. [PMID: 34793617 PMCID: PMC9541358 DOI: 10.1111/cbdd.13983] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/31/2021] [Accepted: 11/06/2021] [Indexed: 12/16/2022]
Abstract
Ginsenoside compound K (CK) is the major intestinal bacterial metabolite of ginsenosides that exhibits anticancer potential in various cancer cells both in vitro and in vivo. The anticancer types, mechanisms, and effects of CK in the past decade have been summarized in this review. Briefly, CK exerts anticancer effects via multiple molecular mechanisms, including the inhibition of proliferation, invasion, and migration, the induction of apoptosis and autophagy, and anti‐angiogenesis. Some signaling pathways play a significant role in related processes, such as PI3K/Akt/mTOR, JNK/MAPK pathway, and reactive oxygen species (ROS). Moreover, the effects of CK combined with nanocarriers for anticancer efficiency are discussed in this review. Furthermore, we aimed to review the research progress of CK against cancer in the past decade, which might provide theoretical support and effective reference for further research on the medicinal value of small molecules, such as CK.
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Affiliation(s)
- Li Zhou
- Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Zhong-Kun Li
- Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Cong-Yuan Li
- Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Yue-Qin Liang
- Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Fan Yang
- Joint Surgery, General Hospital of Tibetan Military Command Lhasa, Lhasa, China
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30
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Jiang X, Wang J, Chen P, He Z, Xu J, Chen Y, Liu X, Jiang J. [6]-Paradol suppresses proliferation and metastases of pancreatic cancer by decreasing EGFR and inactivating PI3K/AKT signaling. Cancer Cell Int 2021; 21:420. [PMID: 34376189 PMCID: PMC8353760 DOI: 10.1186/s12935-021-02118-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/27/2021] [Indexed: 12/17/2022] Open
Abstract
Background The underlying mechanism behind the tumorigenesis and progression of pancreatic cancer is not clear, and treatment failure is generally caused by early metastasis, recurrence, drug resistance and vascular invasion. Exploring novel therapeutic regimens is necessary to overcome drug resistance and improve patients outcomes. Methods Functional assays were performed to investigate the role of [6]-Paradol (6-P) in proliferation and metastasis of pancreatic cancer in vitro and in vivo. The interaction between EGFR and 6-P was tested by KEGG enrichment analysis and molecular docking analysis. qRT-PCR was performed to detect the mRNA expression of EGFR in 6-P treated groups. Involvement of the PI3K/AKT pathway was measured by western blotting. Results 6-P significantly suppressed pancreatic cancer cell proliferation and metastasis. KEGG enrichment analysis and molecular docking analysis suggested that there existed certain interaction between EGFR and 6-P. In addition, 6-P obviously decreased EGFR protein expression level but did not change the mRNA expression level of EGFR. 6-P could induce degradation of EGFR through decreasing the protein stability of EGFR and enhancing the ubiquitin-mediated proteasome-dependent degradation, 6-P-mediated EGFR degradation led to inactivation of PI3K/AKT signaling pathway. However, ectopic expression of EGFR protein resulted in resistance to 6-P-mediated inactivity of PI3K/AKT signaling and inhibition of malignant phenotype of pancreatic cancer. Inversely, erlotinib could enhance the 6-P-mediated anticancer activity. Conclusion Our data indicated that 6-P/EGFR/PI3K/AKT signaling axis might become one of the potential therapies for the treatment of pancreatic cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02118-0.
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Affiliation(s)
- Xueyi Jiang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan City, Hubei Province, 430060, People's Republic of China.,Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Jie Wang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan City, Hubei Province, 430060, People's Republic of China
| | - Peng Chen
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan City, Hubei Province, 430060, People's Republic of China.,Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Zhiwei He
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan City, Hubei Province, 430060, People's Republic of China.,Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Jian Xu
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan City, Hubei Province, 430060, People's Republic of China
| | - Yankun Chen
- Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Xinyuan Liu
- Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Jianxin Jiang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan City, Hubei Province, 430060, People's Republic of China.
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31
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Wang S, Cai Y, Feng Q, Gao J, Teng B. Pseudoginsengenin DQ exerts antitumour activity against hypopharyngeal cancer cells by targeting the HIF-1α-GLUT1 pathway. Cancer Cell Int 2021; 21:382. [PMID: 34281558 PMCID: PMC8287670 DOI: 10.1186/s12935-021-02080-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/06/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Ginsenosides have been reported to possess a variety of biological activities. Synthesized from the ginsenoside protopanaxadiol (PPD), the octanone pseudoginsengenin DQ (PDQ) may have robust pharmacological effects as a secondary ginsenoside. Nevertheless, its antitumour activity and molecular mechanism against hypopharyngeal cancer cells remain unclear. METHODS Cell Counting Kit8 assays, cell cycle assays and cell apoptosis assays were conducted to assess FaDu cell proliferation, cell phase and apoptosis. The interactions between PDQ and HIF-1α were investigated by a molecular docking study. The expression of HIF-1α, GLUT1, and apoptosis-related proteins was detected by Western blotting, direct stochastic optical reconstruction microscopy (dSTORM) and qRT-PCR. A glucose uptake assay was used to assess the glucose uptake capacity of FaDu cells. RESULTS PDQ suppressed proliferation, reduced glucose uptake, and induced cell cycle arrest and apoptosis in FaDu cells. A molecular docking study demonstrated that PDQ could interact with the active site of HIF-1α. PDQ decreased the expression and mRNA levels of HIF-1α and its downstream factor GLUT1. Moreover, the dSTORM results showed that PDQ reduced GLUT1 expression on the cell membrane and inhibited GLUT1 clustering. CONCLUSION Our work showed that the antitumour effect of PDQ was related to the downregulation of the HIF-1α-GLUT1 pathway, suggesting that PDQ could be a potential therapeutic agent for hypopharyngeal cancer treatment.
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Affiliation(s)
- Sanchun Wang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Yu Cai
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Qingjie Feng
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Jing Gao
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
| | - Bo Teng
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, China.
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Yin Q, Chen H, Ma RH, Zhang YY, Liu MM, Thakur K, Zhang JG, Wei ZJ. Ginsenoside CK induces apoptosis of human cervical cancer HeLa cells by regulating autophagy and endoplasmic reticulum stress. Food Funct 2021; 12:5301-5316. [PMID: 34013944 DOI: 10.1039/d1fo00348h] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Ginsenoside CK (GCK), as a metabolite of ginsenoside Rb1, has been studied for its anti-cancer activity. However, its in-depth anti-cancer mechanism on cervical cancer (CC) HeLa cells has not been fully elucidated. This study found that GCK inhibited the proliferation of CC HeLa cells and caused alteration in cell morphology with an IC50 of 45.95 μM. At the same time, GCK treatment blocked the cell cycle in the G0/G1 phase, elevated the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (Δψm), contributed to Ca2+ leakage, inhibited HeLa cell metastasis, and stimulated the key markers related to apoptosis, mitochondrial and endoplasmic reticulum pathways. GCK altered the regulation of the Caspase family, Bak/Bcl-xl and down-regulated the endoplasmic reticulum pathways (PERK and IRE1α). Starting from flow cytometry and the protein level, we found that autophagy inhibitors inhibited autophagy while promoting apoptosis, and apoptosis inhibitors reduced the rate of apoptosis while promoting autophagy, which proved that GCK can be used as a suitable novel natural product for CC treatment.
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Affiliation(s)
- Qi Yin
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China.
| | - Hua Chen
- School of Biology, Food and Environment, Hefei University, Hefei, People's Republic of China.
| | - Run-Hui Ma
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China. and Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan 750021, People's Republic of China
| | - Yuan-Yuan Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China.
| | - Miao-Miao Liu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China.
| | - Kiran Thakur
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China. and Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan 750021, People's Republic of China
| | - Jian-Guo Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China. and Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan 750021, People's Republic of China
| | - Zhao-Jun Wei
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, People's Republic of China. and Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan 750021, People's Republic of China
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