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Tang H, Kang H, Zhou W, Hou T, Guo Z, Liu Y, Xue X, Wang J. Bioactivity-guided isolation of anti-proliferative compounds from Curcuma zedoaria against triple negative breast cancer cells. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2025; 17:2740-2748. [PMID: 40094307 DOI: 10.1039/d5ay00050e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Triple-negative breast cancer (TNBC) presents limited clinically effective treatment options. Curcuma zedoaria (C. zedoaria), a traditional medicine, has been used in China to treat various cancers including TNBC, although its active components remain unclear. Herein, we applied multidimensional liquid chromatography combined with bioactivity assay to discover anti-proliferative compounds against TNBC cells from C. zedoaria. Initially, 26 fractions were generated through first-dimensional reverse-phase liquid chromatography and profiled using SUM159 cells for its anti-proliferative activity. Two active fractions were identified and separated. Following the third-dimensional separation, we successfully isolated two compounds, diarylheptanoid a and diarylheptanoid b, and found that both compounds displayed moderate potency in inhibiting SUM159 proliferation with IC50 values of 19.82 ± 3.08 μM and 28.16 ± 1.97 μM, respectively. Transcriptome analysis revealed that the differentially expressed genes induced by diarylheptanoid a were mainly concentrated with the actin function and involved in motor protein pathways. This study suggests that diarylheptanoids may contribute to the anti-TNBC effects of C. zedoaria and provide potential scaffolds for anti-TNBC drug development.
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Affiliation(s)
- Hongming Tang
- Aquatic Animal Hospital, Dalian Ocean University, Dalian 116023, China.
| | - Hongjian Kang
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Weijia Zhou
- Aquatic Animal Hospital, Dalian Ocean University, Dalian 116023, China.
| | - Tao Hou
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
| | - Zhixin Guo
- Aquatic Animal Hospital, Dalian Ocean University, Dalian 116023, China.
| | - Yanfang Liu
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
| | - Xingya Xue
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
| | - Jixia Wang
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
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Cheng Y, Di YM, May B, Zhang AL, Xue CC, Zhang B. Effects of Chinese herbal medicine on colorectal adenoma recurrence following polypectomy: a systematic review and meta-analysis. Front Pharmacol 2025; 16:1460900. [PMID: 40183090 PMCID: PMC11966114 DOI: 10.3389/fphar.2025.1460900] [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: 07/07/2024] [Accepted: 02/05/2025] [Indexed: 04/05/2025] Open
Abstract
Objective Preventing colorectal adenoma (CRA) recurrence after polypectomy is essential. However, the current evidence of Chinese herbal medicine (CHM) for CRA recurrence is still limited. This study aims to synthesize the effects of CHM as a prevention method for CRA recurrence. Methods Nine databases were searched up to May 2024. Randomised controlled trials identifying the preventive effects of CHM among people with CRA post-polypectomy were included. spreadsheets were used to collect and extract data. RevMan and STATA were used for data analysis. We performed subgroup and sensitivity analyses to explore potentially influencing variables. Results Twenty trials (2,325 participants) were included. The commonly used botanical drugs belonged to the categories of strengthening the spleen and anti-tumour metabolites. Compared to routine care (RC) alone, oral CHM plus RC significantly reduced the CRA recurrence rate at 12 months (RR 0.51, 95% CI [0.39, 0.67], I2 = 42%), 6 months (RR 0.44, 95% CI [0.36, 0.55], I2 = 0%), and 3 months (RR 0.46, 95% CI [0.22, 0.96], I2 = 0%) post-polypectomy. Compared to CHM placebo plus RC, San zi granule combined with RC significantly reduced CRA recurrence at 12 months post-polypectomy (RR 0.39, 95% CI [0.16, 0.93], I2 = 0%) and during the 2-year follow-up (RR 0.73, 95% CI [0.58, 0.90]). There were no significant differences between groups for treatment duration and syndromes. Additional analysis showed that oral CHM containing the botanical drugs of Si jun zi decoction plus RC reduced CRA recurrence at 12 months post-polypectomy with a low heterogeneity, compared to RC alone (RR 0.26, 95% CI [0.13, 0.54], I2 = 0%). Adverse events were similar in the above two comparisons. Conclusion Oral CHM combined with RC may reduce CRA recurrence and be well-tolerated. San zi granule and Si jun zi decoction may be representative prescriptions Experimental studies of the frequent botanical drugs have found anti-cancer effects that may account for the clinical findings. Future rigorous clinical trials are needed due to low-to-moderate certainty of evidence. Systematic Review Registration PROSPERO (CRD42023324197), https://www.crd.york.ac.uk/PROSPERO/view/CRD42023324197.
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Affiliation(s)
- Yi Cheng
- The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia
- Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China
| | - Yuan Ming Di
- The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia
| | - Brian May
- The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia
| | - Anthony Lin Zhang
- The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia
| | - Charlie Changli Xue
- The China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia
- Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China
| | - Beiping Zhang
- Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
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Lu Q, Jiang J, Wang X, Wang R, Han X. Advancements in the Research of Astragalus membranaceus for the Treatment of Colorectal Cancer. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2025; 53:119-146. [PMID: 39880662 DOI: 10.1142/s0192415x25500065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Colorectal cancer, characterized by its high incidence, concealed early symptoms, and poor prognosis at advanced stages, ranks as the third leading cause of cancer-related deaths worldwide. Astragalus membranaceus (AM) refers to the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao and Astragalus membranaceus (Fisch.) Bge. In the theory of Traditional Chinese Medicine (TCM), it is believed to have the functions of tonifying qi and lifting yang, as well as generating body fluids and nourishing blood. It can effectively treat cancer caused by the deficiency of vital energy and susceptibility to external diseases. Modern research has confirmed that the active components of AM, including Astragalus polysaccharides, flavonoids (formononetin and calycosin), Astragalus saponins (Astragaloside I and Astragaloside III), and Astragalus nanovesicles, are effective in the treatment of colorectal cancer. The mechanisms mainly involve inducing apoptosis, inhibiting tumor angiogenesis and the metastasis of cancer cells, regulating the cell cycle and tumor microenvironment, and reversing drug resistance. Moreover, it offers a synergistic enhancement when used in combination with chemotherapy, radiotherapy, targeted therapy, or surgical treatment. AM also has great potential in treating colorectal cancer when combined with other herbs. This review summarizes the relevant research findings on the treatment of colorectal cancer with AM, as well as its main pharmacological effects and molecular mechanisms, aiming to provide guidance for the development of new drugs, and offer direction for the conduct of more related research and promoting the development and application of AM.
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Affiliation(s)
- Qiwen Lu
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine (NJUCM), Nanjing, Jiangsu, P. R. China
| | - Jiaxin Jiang
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine (NJUCM), Nanjing, Jiangsu, P. R. China
| | - Xi Wang
- The First Clinical Medical College, Nanjing University of Chinese Medicine (NJUCM), Nanjing, Jiangsu, P. R. China
| | - Rongling Wang
- Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Deutsches Herzzentrum der Charité (DHZC), Charité - Universitätsmedizin, Berlin, 10115 Berlin, Germany
- Deutsches Zentrum für Herz-Kreislauf-Forschung e. V., (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany
| | - Xuan Han
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine (NJUCM), Nanjing, Jiangsu, P. R. China
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Li J, Niu Y, Yuan L, Jiang W, Jiao T, Dou H, Nan Y. Research Progress in the Medicine-Food Dual Use of Astragalus for Gastrointestinal Tumors. J Med Food 2024; 27:1145-1157. [PMID: 39431943 DOI: 10.1089/jmf.2024.k.0057] [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] [Indexed: 10/22/2024] Open
Abstract
Gastrointestinal tumors have a major impact on human life expectancy and quality of life and are a major cause of personal and social hygiene stress. Gastrointestinal tumors are the main cause of cancer-related death, and the main treatment methods are surgery, radiotherapy, and chemotherapy. However, they also cause great damage to the body and have a poor prognosis after surgery. Therefore, we urgently need safe and effective drugs to intervene in gastrointestinal tumors. In recent years, Traditional Chinese Medicine has been widely used in tumor treatment as a complementary and alternative therapy. Astragalus membranaceus is one of the main herbal medicines with tonic effect and one of the important components of many antitumor herbal compounds. Astragalus polysaccharides, saponins, and flavonoids are the main active components of Astragalus, all of which have antitumor effects. In this article, we studied the mechanism of action of Astragalus and its active ingredients in the intervention of gastrointestinal tumors in recent years and suggested a new approach for the study of Astragalus intervention in gastrointestinal tumors from the perspective of the homology of medicine and food.
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Affiliation(s)
- Jiaqing Li
- Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Yinchuan, China
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, China
| | - Yang Niu
- Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Yinchuan, China
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, China
| | - Ling Yuan
- Pharmacy College of Ningxia Medical University, Yinchuan, China
| | - Wenjie Jiang
- Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Yinchuan, China
| | - Taiqiang Jiao
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, China
| | - Hongli Dou
- Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Yinchuan, China
- Marxist College of Shaanxi University of Chinese Medicine, Xi'an, China
| | - Yi Nan
- Ningxia Medical University Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Yinchuan, China
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Sun R, Sun C, Yue Z, Yin G, Zhou L, Zhang S, Zhang Y, Tang D, Tan X. Astragali Radix-Curcumae Rhizoma herb pair reduces the stemness of colorectal cancer cells through HIF-2α/β-catenin pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155824. [PMID: 38941816 DOI: 10.1016/j.phymed.2024.155824] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 06/02/2024] [Accepted: 06/11/2024] [Indexed: 06/30/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality and significantly impairs quality of life. Astragali Radix-Curcumae Rhizoma (AC) is widely employed in the treatment of CRC in Chinese medicine, but the precise mechanisms remain unclear. PURPOSE This study aimed to elucidate the mechanisms by which AC inhibits CRC progression. METHODS The active components of AC were identified using UPLC-MS/MS analysis. An orthotopic transplantation colorectal tumor model was established in BALB/c mice using the CT26-Lucifer cell line to evaluate the effects of AC. Tumor volumes were monitored using IVIS imaging technology. Histological examination of tumor morphology was performed with hematoxylin and eosin (H&E) staining. Transcriptomic sequencing of mouse tumor samples was conducted to identify critical pathways and molecular targets. The impact of AC on cell viability and migration was assessed using CCK-8 and wound healing assays, respectively. To investigate the effects of AC on CRC cells, an in vitro hypoxic model was established using cobalt chloride (CoCl2), a hypoxia inducer. HIF-2α overexpression was achieved by constructing stable lentiviral vectors. Key targets identified from RNA-seq, such as c-Myc, Ki-67, β-catenin, cleaved caspase 3, CD133, and CD44, were evaluated using western blotting, qRT-PCR, and immunofluorescence assays. Epithelial-Mesenchymal Transition (EMT) and spheroid cloning assays were employed to evaluate phenotypic changes in cancer stem cells. RESULTS Twelve components of AC were identified. AC effectively inhibited CRC progression in vivo. Transcriptomic analysis highlighted hypoxic signaling as a significantly enriched pathway, implicating its role in suppressing CRC progression by AC. In the hypoxic model, AC inhibited the proliferation and migration of CRC cells in vitro. Furthermore, AC reduced cancer stemness by downregulating stemness markers, inhibiting EMT, and decreasing tumor sphere formation. The downregulation of hypoxic responses and the shift in stemness by AC involved attenuation of HIF-2α and WNT/β-catenin signaling. CONCLUSION This study provides the first evidence that AC reduces the stemness of CRC and the inhibition of the transition of CRC to stem-like cells by AC is closely related to the downregulation of the HIF-2α/β-catenin pathway, especially under hypoxic conditions.
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Affiliation(s)
- Ruiqian Sun
- Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Cheng Sun
- Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Zengyaran Yue
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Gang Yin
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Lingling Zhou
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Shuo Zhang
- Department of Pharmacy, Nantong Hospital of Traditional Chinese Medicine, Affiliated with Nanjing University of Chinese Medicine, Nantong, 226007, China
| | - Yu Zhang
- State Key Laboratory of Reproductive Medicine, Department of Clinic Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
| | - Decai Tang
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Xiying Tan
- Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
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Zhang Y, Chen Z, Chen L, Dong Q, Yang DH, Zhang Q, Zeng J, Wang Y, Liu X, Cui Y, Li M, Luo X, Zhou C, Ye M, Li L, He Y. Astragali radix (Huangqi): a time-honored nourishing herbal medicine. Chin Med 2024; 19:119. [PMID: 39215362 PMCID: PMC11363671 DOI: 10.1186/s13020-024-00977-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.
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Affiliation(s)
- Yuyu Zhang
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Zhejie Chen
- Institute of Molecular Medicine (IMM), Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Liping Chen
- School of Comprehensive Health Management, Xihua University, Chengdu, 610039, China
| | - Qin Dong
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Dong-Hua Yang
- New York College of Traditional Chinese Medicine, Mineola, NY, 11501, USA
| | - Qi Zhang
- Pengzhou Hospital of Traditional Chinese Medicine, Pengzhou, 611930, China
| | - Jing Zeng
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Yang Wang
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Xiao Liu
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Yuan Cui
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Minglong Li
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Xiao Luo
- Chengdu Institute for Drug Control, NMPA Key Laboratory for Quality Monitoring and Evaluation of Traditional Chinese Medicine, Chengdu, 610045, China
| | - Chongjian Zhou
- HuBei Guizhenyuan Chinese Herbal Medicine Co.Ltd., Hong'an, 438400, China
| | - Mingzhu Ye
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China
| | - Ling Li
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China.
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
| | - Yuxin He
- School of Food and Bioengineering, Xihua University, Chengdu, 610039, China.
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Yang L, Liu J, Zhang J, Shao F, Jin Y, Xing J, Zhou H, Yu A. Anticancer effects of Erzhimaoling decoction in high-grade serous ovarian cancer in vitro and in vivo. Eur J Med Res 2024; 29:405. [PMID: 39103890 PMCID: PMC11299366 DOI: 10.1186/s40001-024-01968-4] [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: 05/29/2024] [Accepted: 07/10/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo. MATERIALS AND METHODS EZMLD-containing serum was prepared from Sprague-Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC50. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks. RESULTS In vitro, EZMLD-containing serum had IC50 values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression. CONCLUSIONS EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.
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MESH Headings
- Ovarian Neoplasms/drug therapy
- Ovarian Neoplasms/pathology
- Neoplasm Grading
- Drugs, Chinese Herbal/pharmacology
- Drugs, Chinese Herbal/therapeutic use
- Rats, Sprague-Dawley
- Cell Line, Tumor
- Humans
- Female
- Animals
- Rats
- Methyltransferases/genetics
- Methyltransferases/metabolism
- Gene Knockdown Techniques
- Inhibitory Concentration 50
- Cell Survival/drug effects
- Apoptosis/drug effects
- Xenograft Model Antitumor Assays
- Gene Expression Regulation, Neoplastic/drug effects
- Keratin-8/metabolism
- Antineoplastic Agents, Phytogenic/pharmacology
- Antineoplastic Agents, Phytogenic/therapeutic use
- Carcinoma, Ovarian Epithelial/drug therapy
- Carcinoma, Ovarian Epithelial/pathology
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Specific Pathogen-Free Organisms
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Affiliation(s)
- Li Yang
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China
| | - Jingfang Liu
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China
| | - Jiejie Zhang
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China
| | - Feng Shao
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China
| | - Yanlu Jin
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China
| | - Jie Xing
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China
| | - Heran Zhou
- Department of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, Zhejiang, China.
| | - Aijun Yu
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, 310022, Zhejiang, China.
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Li Q, Kong ZD, Wang H, Gu HH, Chen Z, Li SG, Chen YQ, Cai Y, Yang ZJ. Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase. Chin J Integr Med 2024; 30:499-506. [PMID: 37612478 DOI: 10.1007/s11655-023-3702-4] [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] [Accepted: 03/01/2023] [Indexed: 08/25/2023]
Abstract
OBJECTIVE To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. METHODS A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg-1•d-1), MPA + low-dose (20 mg•kg-1•d-1) JP (L-JP), MPA + medium-dose (30 mg•kg-1•d-1) JP (M-JP), and MPA + high-dose (40 mg•kg-1•d-1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. RESULTS JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. CONCLUSIONS Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system).
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Affiliation(s)
- Qi Li
- Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China
| | - Zhao-di Kong
- College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou, 510632, China
| | - Huan Wang
- College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou, 510632, China
| | - Hong-Hui Gu
- Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China
| | - Zhong Chen
- Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China
| | - Shi-Guang Li
- Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China
| | - Yi-Qi Chen
- Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China
| | - Yu Cai
- College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou, 510632, China
- Guangdong Key Lab of Traditional Chinese Medicine Information Technology, Jinan University, Guangzhou, 510632, China
| | - Zhen-Jiang Yang
- Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China.
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Fang F, Jin X, Meng J, He J, Wang J, Wang C, Xie S, Shi W. Jiedu Fuzheng decoction improves the proliferation, migration, invasion and EMT of non-small cell lung cancer via the Wnt/β-catenin pathway. Cell Div 2023; 18:22. [PMID: 38104091 PMCID: PMC10725601 DOI: 10.1186/s13008-023-00105-7] [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: 10/18/2023] [Accepted: 12/11/2023] [Indexed: 12/19/2023] Open
Abstract
OBJECTIVES This study aimed to investigate the effect of Jiedu Fuzheng decoction (JFD) in non-small cell lung cancer (NSCLC) and its potential therapeutic mechanism. RESULTS We prepared JFD-medicated serum from rats and treated NSCLC cells (A549 and NCI-H1650) with 0.5, 1, and 2 mg/mL JFD-medicated serum. CCK-8 and colony formation assays were used to detect cell proliferation. Transwell assays showed that JFD attenuated cell migration and invasion. JFD and SKL2001 (Wnt/β-catenin activator) were simultaneously used to treat NSCLC cells to verify that JFD regulated the biological behavior of NSCLC via Wnt/β-catenin signaling. It was found that 2 mg/mL JFD had the most significant effect on the activity of NSCLC cells. JFD attenuated proliferation and metastasis but increased the proportion of apoptotic cells. At the same time, JFD downregulated N-cadherin, vimentin and β-catenin protein expression in cancer cells. SKL2001 could restore the improvement of JFD on proliferation, metastasis and apoptosis. CONCLUSION This study confirmed that JFD suppressed the occurrence and development of NSCLC by regulating Wnt/β-catenin signaling and provided a novel therapeutic scheme for NSCLC.
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Affiliation(s)
- Fang Fang
- The Second Ward of Oncology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 327, Xianhu Avenue, Qingxiu District, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Xiaowei Jin
- Department of Traditional Chinese Medicine, Yunnan Cancer Hospital, Kunming, 650018, Yunnan, People's Republic of China
| | - Jinming Meng
- Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Jiaqi He
- Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Jiaxiao Wang
- The Second Ward of Oncology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 327, Xianhu Avenue, Qingxiu District, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Changhong Wang
- The Second Ward of Oncology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 327, Xianhu Avenue, Qingxiu District, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Sheng Xie
- Preventive Treatment of Disease Center, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89-9, Dongge Road, Qingxiu District, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China.
| | - Wei Shi
- The Second Ward of Oncology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 327, Xianhu Avenue, Qingxiu District, Nanning, 530001, Guangxi Zhuang Autonomous Region, People's Republic of China.
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10
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Jia W, Yuan J, Cheng B, Ling C. Targeting tumor-derived exosome-mediated premetastatic niche formation: The metastasis-preventive value of traditional Chinese medicine. Cancer Lett 2023:216261. [PMID: 37302563 DOI: 10.1016/j.canlet.2023.216261] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 06/02/2023] [Accepted: 06/02/2023] [Indexed: 06/13/2023]
Abstract
Tumor-derived exosome (TDE)-mediated premetastatic niche (PMN) formation is a potential mechanism underlying the organotropic metastasis of primary tumors. Traditional Chinese medicine (TCM) has shown considerable success in preventing and treating tumor metastasis. However, the underlying mechanisms remain elusive. In this review, we discussed PMN formation from the perspectives of TDE biogenesis, cargo sorting, and TDE recipient cell alterations, which are critical for metastatic outgrowth. We also reviewed the metastasis-preventive effects of TCM, which act by targeting the physicochemical materials and functional mediators of TDE biogenesis, regulating the cargo sorting machinery and secretory molecules in TDEs, and targeting the TDE-recipient cells involved in PMN formation.
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Affiliation(s)
- Wentao Jia
- Oncology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China; Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200043, China.
| | - Jiaying Yuan
- Oncology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China; Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200043, China.
| | - Binbin Cheng
- Oncology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China; Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200043, China.
| | - Changquan Ling
- Oncology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China; Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200043, China.
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11
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Liang ZQ, Bian Y, Gu JF, Yin G, Sun RL, Liang Y, Wan LL, Yin QH, Wang X, Gao J, Zhao F, Tang DC. Exploring the anti-metastatic effects of Astragalus mongholicus Bunge-Curcuma aromatica Salisb. on colorectal cancer: A network-based metabolomics and pharmacology approach. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 114:154772. [PMID: 37015187 DOI: 10.1016/j.phymed.2023.154772] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/28/2023] [Accepted: 03/14/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) is a common malignancy that can significantly diminish patients' quality of life. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is an ancient Chinese medicinal combination used for the treatment of CRC. However, the core ingredients and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. We aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods. METHODS Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in the feces and serum of CRC mice. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC-target-component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction. RESULTS AC, high-dose AC, and 5-fluorouracil treatment reduced liver metastasis and tumor mass. Compared with the CRC group, 2 amino acid metabolites and 14 lipid metabolites (LPC, PC, PE) were upregulated and 15 amino acid metabolites and 9 lipid metabolites (TG, PE, PG, 12-HETE) were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-Elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors. CONCLUSION Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.
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Affiliation(s)
- Zhong Qing Liang
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Yong Bian
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China; Laboratory Animal Center, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Jun Fei Gu
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Gang Yin
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Ruo Lan Sun
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Yan Liang
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Lin Lu Wan
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Qi Hang Yin
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Xu Wang
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - Jin Gao
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China; School of Acupuncture and Tuina, School of Health and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu, China
| | - Fan Zhao
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
| | - De Cai Tang
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China.
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12
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Qiao D, Liu XY, Zheng L, Zhang YL, Que RY, Ge BJ, Cao HY, Dai YC. Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types. World J Clin Cases 2023; 11:1963-1973. [PMID: 36998954 PMCID: PMC10044969 DOI: 10.12998/wjcc.v11.i9.1963] [Citation(s) in RCA: 2] [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: 11/22/2022] [Revised: 02/12/2023] [Accepted: 03/03/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, with the fourth highest mortality among all cancers. Reportedly, in addition to adenomas, serrated polyps, which account for 15%-30% of CRCs, can also develop into CRCs through the serrated pathway. Sessile serrated adenomas/polyps (SSAs/Ps), a type of serrated polyps, are easily misdiagnosed during endoscopy. AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types. METHODS From January 2021 to December 2021, patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital, affiliated with Shanghai University of Traditional Chinese Medicine. Thirty cases each of large intestine damp-heat (Da-Chang-Shi-Re, DCSR) syndrome and spleen-stomach weakness (Pi-Wei-Xu-Ruo) syndrome were reported. Baseline comparison of the general data, typical tongue coating, colonoscopy findings, and hematoxylin and eosin findings was performed in each group. The expression of the Wnt pathway-related proteins, namely β-catenin, adenomatous polyposis coli, and mutated in colorectal cancer, were analyzed using immunohistochemistry. RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types (P = 0.001). The other aspects did not differ between the two groups. The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups, which was manifested as β-catenin protein translocation into the nucleus. However, SSAs/Ps patients with DCSR syndrome had more nucleation, higher β-catenin expression, and negative regulatory factor (adenomatous polyposis coli and mutated in colorectal cancer) expression (P < 0.0001) than SSA/P patients with Pi-Wei-Xu-Ruo syndrome. In addition, the SSA/P size was linearly correlated with the related protein expression. CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis. A high-quality colonoscopic diagnosis was essential. The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.
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Affiliation(s)
- Dan Qiao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Xiao-Yan Liu
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Lie Zheng
- Department of Gastroenterology, Traditional Chinese Medicine Hospital of Xi’an, Xi’an 730000, Shaanxi Province, China
| | - Ya-Li Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Ren-Ye Que
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Bing-Jing Ge
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Hong-Yan Cao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
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Yang X, Peng Y, Wang YE, Zheng Y, He Y, Pan J, Liu N, Xu Y, Ma R, Zhai J, Ma Y, Guan S. Curcumae Rhizoma Exosomes-like nanoparticles loaded Astragalus components improve the absorption and enhance anti-tumor effect. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
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14
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Chen Y, Chen M, Deng K. Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review). Int J Oncol 2022; 62:24. [PMID: 36579676 PMCID: PMC9854240 DOI: 10.3892/ijo.2022.5472] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 12/02/2022] [Indexed: 12/28/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumor types occurring in the digestive system. The incidence of CRC has exhibits yearly increases and the mortality rate among patients with CRC is high. The Wnt/β‑catenin signaling pathway, which is associated with carcinogenesis, is abnormally activated in CRC. Most patients with CRC have adenomatous polyposis coli mutations, while half of the remaining patients have β‑catenin gene mutations. Therefore, targeting the Wnt/β‑catenin signaling pathway for the treatment of CRC is of clinical value. In recent years, with in‑depth research on the Wnt/β‑catenin signaling pathway, inhibitors have been developed that are able to suppress or hinder the development and progression of CRC. In the present review, the role of the Wnt/β‑catenin signaling pathway in CRC is summarized, the research status on Wnt/β‑catenin pathway inhibitors is outlined and potential targets for inhibition of this pathway are presented.
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Affiliation(s)
- Yuxiang Chen
- Department of Gastroenterology and Hepatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China,The Laboratory of Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Mo Chen
- Department of Gerontology, Tibetan Chengdu Branch Hospital of West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China,Department of Gerontology, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, Sichuan 610041, P.R. China,Professor Mo Chen, Department of Gerontology, Tibetan Chengdu Branch Hospital of West China Hospital, Sichuan University, 20 Ximianqiao Cross Street, Chengdu, Sichuan 610041, P.R. China, E-mail:
| | - Kai Deng
- Department of Gastroenterology and Hepatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China,The Laboratory of Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China,Correspondence to: Professor Kai Deng, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041, P.R. China, E-mail:
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15
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Zhang Q, Gao L, Huang S, Liang Y, Hu J, Zhang Y, Wei S, Hu X. Cocktail of Astragalus Membranaceus and Radix Trichosanthis Suppresses Melanoma Tumor Growth and Cell Migration Through Regulation of Akt-Related Signaling Pathway. Front Pharmacol 2022; 13:880215. [PMID: 35721145 PMCID: PMC9198299 DOI: 10.3389/fphar.2022.880215] [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: 02/21/2022] [Accepted: 04/11/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Malignant melanoma has high morbidity and mortality and limited treatment options. Traditional Chinese medicine has great potential in the clinical therapy of cancer, and the theory of compatibility is one core content of Chinese medical theory. Astragalus Membranaceus and Radix Trichosanthis are clinically effective for the treatment of various cancers. Methods: We verified the effects of AMD, RTD, and their “cocktail” on melanoma model in vitro and in vivo and the mechanism of its effect on the Akt-related signaling pathway by network pharmacology, MTT, flow cytometry, LDH, SOD, MDA assay, and Western blot. Results: The network pharmacology analysis indicated that the PI3K-Akt pathway plays a crucial role in the treatment of malignant melanoma with these two herbs. In addition, AMD, RTD, and their “cocktail” could inhibit the proliferation of A375 cells by reducing the survival rate in a concentration-dependent manner and by regulating the cell cycle, and the compatibility of two herbs also could inhibit melanoma growth. They could, respectively, induce apoptosis and inhibit migration by affecting the expression of Bcl-2, Bax, p53, snail, E-cadherin, and N-cadherin. Furthermore, LDH activity was decreased, while SOD increased and MDA reduced. The factors of the Akt-related signaling pathway, Akt and p-Akt, were decreased. Conclusion: This study showed that AMD, RTD, and their “cocktail” could regulate cell proliferation, apoptosis, and metastasis in A375 cells through the suppression of the Akt-related signaling pathway, and the “cocktail” groups had detoxification and additive effects. The best compatibility of the two herbs also can inhibit tumor growth and metastasis in vivo.
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Affiliation(s)
- Qiuyan Zhang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Gao
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Songli Huang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yuxi Liang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jingyan Hu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yuan Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Shengli Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiuhua Hu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.,Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
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16
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Hu S, Ge M, Zhang S, Jiang M, Hu K, Gao L. Integrated Network Pharmacology and Experimental Verification to Explore the Molecular Mechanism of Hedysarum Multijugum Maxim-Curcumae Rhizoma Herb Pair for Treating Non-Small Cell Lung Cancer. Front Oncol 2022; 12:854596. [PMID: 35433443 PMCID: PMC9007519 DOI: 10.3389/fonc.2022.854596] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 02/28/2022] [Indexed: 12/18/2022] Open
Abstract
Background Hedysarum Multijugum Maxim–Curcumae Rhizoma (HMMCR), a well-known herb pair in traditional Chinese medicine (TCM), has been widely used for the treatment of various cancers. However, the active components of HMMCR and the underlying mechanism of HMMCR for non-small-cell lung carcinoma (NSCLC) remain unclear. Methods Active ingredients of HMMCR were detected by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). On this basis, potential targets of HMMCR were obtained from SwissTargetPrediction database. NSCLC-related targets were collected from four public databases (GeneCards, OMIM, TTD, and PharmGkb). The drug ingredients–disease targets network was visualized. The hub targets between HMMCR and NSCLC were further analyzed by protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, the results predicted by network pharmacology were further validated via in vitro experiments. Results A total of 181 compounds were identified from the aqueous extract of HMMCR. Through network analysis, a compound–target network including 153 active ingredients of HMMCR and 756 HMMCR-NSCLC co-targets was conducted; 6 crucial compounds and 62 hub targets were further identified. The results of KEGG enrichment analysis showed that PI3K/Akt signaling pathway may be the critical pathway of HMMCR in the treatment of NSCLC. The in vitro experiments indicated that HMMCR inhibits the proliferation and migration of NSCLC cells via inactivation of the PI3K/Akt signaling pathway, consistent with the results predicted by network pharmacology. Conclusion Integrating LC-ESI-MS/MS, network pharmacology approach, and in vitro experiments, this study shows that HMMCR has vital therapeutic effect on NSCLC through multi-compound, multi-target, and multi-pathway, which provides a rationale for using HMMCR for the treatment of NSCLC.
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Affiliation(s)
- Shaopu Hu
- Beijing University of Chinese Medicine, Beijing, China.,Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Mengxue Ge
- Department of Integrated Management, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Shuixiu Zhang
- Beijing University of Chinese Medicine, Beijing, China.,Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Min Jiang
- Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.,Department of Integrated Management, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Kaiwen Hu
- Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Gao
- Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
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Zhao M, Fu Y, Liu L, Hou Y, Shi M, Zhou H, Zhang G. Identification of Key Drug Targets and Molecular Mechanisms of Curcumae Rhizoma Acting on HBV-Related HCC: Weighted Correlation Network and Network Pharmacological Analyses. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:5399766. [PMID: 35388301 PMCID: PMC8977297 DOI: 10.1155/2022/5399766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/06/2022] [Accepted: 03/10/2022] [Indexed: 12/24/2022]
Abstract
Background Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has poor prognosis and high mortality rate. Curcumae Rhizoma, a classic Chinese medicinal herb, is often used to treat tumors. Methods Active ingredients of Curcumae Rhizoma were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database, and potential targets were predicted by the TCMSP database and Swiss Target Prediction database. The key drug targets were filtered by intersecting predicted targets, DEGs, and genes in important modules from WGCNA. Besides, the key drug targets were used to construct a network of "herb-active ingredient-target-disease" interactions and subjected to enrichment analysis and protein-protein interaction (PPI) analysis. The hub targets based on PPI analysis was evaluated by the KMplotter database. Results Three active ingredients of Curcumae Rhizoma were collected with OB ≥ 30% and DL ≥ 0.18, including hederagenin, wenjine, and bisdemethoxycurcumin. The key drug targets were mainly enriched in cell cycle checkpoint, DNA integrity checkpoint, and peptidyl-serine modification. Besides, Curcumae Rhizoma treatment of HBV-related HCC mainly involved the p53 signaling pathway and arachidonic acid metabolism. Finally, ESR1 and PTGS2 were identified as hub targets from PPI analysis. ESR1 was found to be correlated with survival in liver cancer patients with hepatitis. Conclusion Based on WGCNA and network pharmacological analysis, our results illustrated that Curcumae Rhizoma might work through regulating multitargets and multipathways in HBV-related HCC.
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Affiliation(s)
| | - Yun Fu
- Anhui University of Chinese Medicine, Hefei, China
| | - Lili Liu
- Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Yong Hou
- Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Mei Shi
- Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Hao Zhou
- Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Guoliang Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
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