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Feng H, Yang Y, Chen H, Zhang Z, Zeng J, Huang Y, Yang X, Yang L, Du J, Cao Z. Jiedu Xiaozheng Yin extract targets cancer stem cells by Wnt signaling pathway in colorectal cancer. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118710. [PMID: 39197803 DOI: 10.1016/j.jep.2024.118710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/01/2024] [Accepted: 08/17/2024] [Indexed: 09/01/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The clinical application of the traditional Chinese medicinal formula Jiedu Xiaozheng Yin (JXY) for gastrointestinal tumors, particularly colorectal cancer (CRC), is well-established, yet the precise biological mechanism underlying its efficacy in CRC treatment remains elusive. AIMS OF THE STUDY This study endeavors to unravel the intricate mechanism through which JXY modulates colorectal cancer stem cells, thus elucidating the pathways by which it exerts its potent anti-tumor effects. MATERIALS AND METHODS In this study, the regulatory impact of JXY on the signaling pathway and function of CRC cells was analyzed through Network pharmacology. The ethyl acetate extract of JXY was detected the major compounds using HPLC and then treated the HCT-116 cells for RNA-Sequencing (RNA-Seq). Protein expression and stemness of HCT-15 and HCT-116 cells following JXY extract treatment were assessed using Western blot analysis and matrigel spheroid assays. Additionally, the β-catenin transcriptional activity was evaluated using a TOPflash reporter assay with or without Lithium chloride (LiCl) stimulation. Patient-derived organoids of CRC (CRC PDOs) were cultured using a stemness maintenance medium, and their viability was measured using ATP assays after treatment of JXY extract. Furthermore, the anti-tumor efficacy of JXY extract was assessed using a xenograft mice model derived from HCT-15 cells. RESULTS Network pharmacology emphasized the influence of JXY on cancer stem cells and the Wnt signaling pathway. HPLC analysis confirmed that the JXY extract contained the three most prevalent pharmaceutical compounds among the four herbs documented in the Chinese Pharmacopoeia (rosmarinic acid, quercetin, and kaempferol). RNA-Seq results further elucidated the effect of JXY extract, particularly targeting cancer stem cells and the Wnt signaling pathway. Furthermore, JXY extract inhibited spheroid formation in CRC cells and downregulated CRC CSC markers (CD133, DCLK1, and C-MYC). Additionally, JXY extract suppressed the β-catenin expression and transcriptional activity as well as the Wnt pathway target proteins, including C-MYC and Cyclin D1. Consistent with findings from cell lines, JXY extract suppressed the growth of CRC PDOs exhibiting stemness characteristics. And JXY extract demonstrated a significant inhibitory effect on tumor growth, C-MYC, and β-catenin protein levels in xenograft tumors. CONCLUSIONS These results highlight the novel function of JXY extract in targeting CRC CSCs by regulating Wnt signaling pathway, underscoring its potential as a therapeutic agent for treating CRC.
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Affiliation(s)
- Hailan Feng
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
| | - Yuping Yang
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
| | - Hong Chen
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
| | - Zhuqing Zhang
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
| | - Jianwei Zeng
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
| | - Yunmei Huang
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
| | - Xiaoting Yang
- Talent Research Institute, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
| | - Liu Yang
- School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
| | - Jian Du
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
| | - Zhiyun Cao
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Key Laboratory of Integrative Medicine, Fujian Province University, Fuzhou, 350122, China.
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Zhuang J, Mo J, Huang Z, Yan Y, Wang Z, Cao X, Yang C, Shen B, Zhang F. Mechanisms of Xiaozheng decoction for anti-bladder cancer effects via affecting the GSK3β/β-catenin signaling pathways: a network pharmacology-directed experimental investigation. Chin Med 2023; 18:104. [PMID: 37608369 PMCID: PMC10464372 DOI: 10.1186/s13020-023-00818-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 08/12/2023] [Indexed: 08/24/2023] Open
Abstract
PURPOSE The combination of Xiaozheng decoction with postoperative intravesical instillation has been shown to improve the prognosis of bladder cancer patients and prevent recurrence. However, the mechanisms underlying the efficacy of this herbal formula remain largely unclear. This research aims to identify the important components of Xiaozheng decoction and explore their anti-bladder cancer effect and mechanism using network pharmacology-based experiments. METHODS The chemical ingredients of each herb in the Xiaozheng decoction were collected from the Traditional Chinese Medicine (TCM) database. Network pharmacology was employed to predict the target proteins and pathways of action. Disease databases were utilized to identify target genes associated with bladder cancer. A Protein-Protein Interaction (PPI) network was constructed to illustrate the interaction with intersected target proteins. Key targets were identified using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. A compound-target-pathway network was established after molecular docking predictions. In vitro experiments with bladder cancer cell lines were conducted using core chemical components confirmed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to verify the conclusions of network pharmacology. RESULTS 45 active compounds were extracted, and their relationships with Traditional Chinese Medicines (TCMs) and protein targets were presented, comprising 7 herbs, 45 active compounds, and 557 protein targets. The intersection between potential TCM target genes and bladder cancer-related genes yielded 322 genes. GO and KEGG analyses indicated that these targets may be involved in numerous cancer-related pathways. Molecular docking results showed that candidate compounds except mandenol could form stable conformations with the receptor. In vitro experiments on three bladder cancer cell lines demonstrated that quercetin and two other impressive new compounds, bisdemethoxycurcumin (BDMC) and kumatakenin, significantly promoted cancer cell apoptosis through the B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/BAX) pathway and inhibited proliferation and migration through the glycogen synthase kinase 3 beta (GSK3β)/β-catenin pathway. CONCLUSION By employing network pharmacology and conducting in vitro experiments, the mechanism of Xiaozheng decoction's effect against bladder cancer was tentatively elucidated, and its main active ingredients and targets were identified, providing a scientific basis for future research.
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Affiliation(s)
- Jingming Zhuang
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiahang Mo
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
| | - Zhengnan Huang
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yilin Yan
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zeyi Wang
- Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China
| | - Xiangqian Cao
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chenkai Yang
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bing Shen
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Fang Zhang
- Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Wang R, Fan H, Sun M, Lv Z, Yi W. Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma. Technol Cancer Res Treat 2022; 21:15330338211070689. [PMID: 35072573 PMCID: PMC8793120 DOI: 10.1177/15330338211070689] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Liver cancer has high rates of morbidity and mortality, and its treatment is a global health challenge. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancer cases. B-lymphoma Mo-MLV insertion region 1 (BMI1) has been identified as a proto-oncogene, which contributes to the initiation and progression of many malignant tumors. BMI1 expression is upregulated in HCC, and it influences the occurrence and development of HCC by various mechanisms, such as the INK4a/ARF locus, NF-κB signaling pathway, and PTEN/PI3K/AKT signaling pathway. In addition, the expression of BMI1 is related to prognosis and recurrence of HCC. Hence, there is clear evidence that BMI1 is a novel and valid therapeutic target for HCC. Accordingly, the development of therapeutic strategies targeting BMI1 has been a focus of recent research, providing new directions for HCC treatment. This review summarizes the role of BMI1 in the occurrence and treatment of HCC, which will provide a basis for using BMI1 as a potential target for the development of therapeutic strategies for HCC.
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Affiliation(s)
- Ru Wang
- 278245Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hengwei Fan
- 535219The Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China
| | - Ming Sun
- 278245Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhongwei Lv
- 278245Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wanwan Yi
- 278245Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
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Gnocchi D, Castellaneta F, Cesari G, Fiore G, Sabbà C, Mazzocca A. Treatment of liver cancer cells with ethyl acetate extract of Crithmum maritimum permits reducing sorafenib dose and toxicity maintaining its efficacy. J Pharm Pharmacol 2021; 73:1369-1376. [PMID: 34014301 DOI: 10.1093/jpp/rgab070] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 04/19/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) is one of the most frequent tumours worldwide and available drugs are inadequate for therapeutic results and tolerability. Hence, novel effective therapeutic tools with fewer side effects are of paramount importance. We have previously shown that Crithmum maritimum ethyl acetate extract exerts a cytostatic effect in HCC cells. Here, we tested whether C. maritimum ethyl acetate extract in combination with half sorafenib IC50 dose ameliorated efficacy and toxicity of sorafenib in inhibiting liver cancer cell growth. Moreover, we investigated the mechanisms involved. METHODS Two HCC cell lines (Huh7 and HepG2) were treated with C. maritimum ethyl acetate extract and half IC50 sorafenib dose usually employed in vitro. Then, cell proliferation, growth kinetics and cell toxicity were analysed together with an investigation of the cellular mechanisms involved, focusing on cell cycle regulation and apoptosis. KEY FINDINGS Results show that combined treatment with C. maritimum ethyl acetate extract and half IC50 sorafenib dose decreased cell proliferation comparably to full-dose sorafenib without increasing cell toxicity as confirmed by the effect on cell cycle regulation and apoptosis. CONCLUSIONS These results provide scientific support for the possibility of an effective integrative therapeutic approach for HCC with fewer side effects on patients.
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Affiliation(s)
- Davide Gnocchi
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy
| | - Francesca Castellaneta
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy
| | - Gianluigi Cesari
- International Centre for Advanced Mediterranean Agronomic Studies - CHIEAM, Valenzano (BA), Italy
| | - Giorgio Fiore
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy
| | - Carlo Sabbà
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy
| | - Antonio Mazzocca
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy
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1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth. Sci Rep 2021; 11:1259. [PMID: 33441568 PMCID: PMC7806899 DOI: 10.1038/s41598-020-78867-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 11/24/2020] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By 1H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours.
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Esposito T, Mencherini T, Del Gaudio P, Auriemma G, Franceschelli S, Picerno P, Aquino RP, Sansone F. Design and Development of Spray-Dried Microsystems to Improve Technological and Functional Properties of Bioactive Compounds from Hazelnut Shells. Molecules 2020; 25:molecules25061273. [PMID: 32168873 PMCID: PMC7144004 DOI: 10.3390/molecules25061273] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/06/2020] [Accepted: 03/09/2020] [Indexed: 12/11/2022] Open
Abstract
An extract obtained from hazelnut shells by-products (HSE) has antioxidant and chemopreventive effects on human melanoma and cervical cancer cell lines, inducing apoptosis by caspase-3 activation. A clinical translation is limited by poor water solubility and low bioavailability. Dried plant extracts often show critical characteristics such as sticky/gummy appearance, unpleasant smell, and instability involving practical difficulties in processing for industrial use. A spray drying method has been applied to transform raw HSE in a microparticulate powder. The biopolymeric matrix was based on l-proline as loading carrier, hydroxyethylcellulose in combination with pectin as coating polymers; lecithin and ethanol were used as solubility enhancers. A Hot-Cold-Hot method was selected to prepare the liquid feed. The thus prepared powder showed good technological properties (solid-state, particle dimensions, morphology, and water dissolution rate), stability, and unchanged chemopreventive effects with respect to the unprocessed HSE.
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Affiliation(s)
| | - Teresa Mencherini
- Correspondence: (T.M.); (F.S.); Tel.: +39-089-968294 (T.M.); +39-089-968146 (F.S.)
| | | | | | | | | | | | - Francesca Sansone
- Correspondence: (T.M.); (F.S.); Tel.: +39-089-968294 (T.M.); +39-089-968146 (F.S.)
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Gnocchi D, Cesari G, Calabrese GJ, Capone R, Sabbà C, Mazzocca A. Inhibition of Hepatocellular Carcinoma Growth by Ethyl Acetate Extracts of Apulian Brassica oleracea L. and Crithmum maritimum L. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2020; 75:33-40. [PMID: 31741122 DOI: 10.1007/s11130-019-00781-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Nowadays, a growing body of evidence supports the view that plants offer an extraordinary opportunity to discover and develop new promising therapeutic strategies for many diseases, including cancer. Here we tested the anticancer action against Hepatocellular carcinoma (HCC) of extracts obtained from two plants harvested in Apulia, namely Brassica oleracea L. and Crithmum maritimum L. B. oleracea was grown in biodynamical agriculture without any agrochemical input, instead C. maritimum was collected on Apulian coasts and is still commonly eaten in Apulia. HCC, one of the most frequent tumors worldwide, is estimated to become the third leading cause of cancer-related deaths in Western Countries by 2030. The approved synthetic drugs for the treatment of HCC are currently inadequate in terms of therapeutic results and tolerability. Hence, aim of the present study was to test the anticancer action against HCC of extracts obtained from Brassica oleracea L. and Crithmum maritimum L. We preliminary prepared extracts from both plants using four solvents with different polarity: hexane, ethyl acetate, methanol and ethanol. Then, we tested the effect of the different fractions in inhibiting HCC cell growth. Finally, we characterized the mechanism of action of the most effective fraction. We found that ethyl acetate fractions from both plants were the most effective in inhibiting HCC growth. In particular, we demonstrated that these fractions effectively reduce HCC growth by exerting, on one hand, a cytostatic effect through their action on the cell cycle, and on the other hand by triggering apoptosis and necrosis. Our findings support the notion that ethyl acetate fractions from Apulian B. oleracea and C. maritimum can be in perspective considered as promising tools to expand the opportunities to identify new and not toxic anticancer therapeutic approaches for HCC. Further pharmacological investigations will shed light on how this could be effectively achieved. Graphical Abstract Experimental workflow for the detection of the ethyl acetate extract of Brassica oleracea L. and Crithmum maritimum L. as an active fraction in inhibiting HCC cell growth.
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Affiliation(s)
- Davide Gnocchi
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy
| | - Gianluigi Cesari
- Department of Organic Agriculture, CIHEAM - Mediterranean Agronomic Institute of Bari, 70010, Valenzano, BA, Italy
| | - Generosa Jenny Calabrese
- Department of Organic Agriculture, CIHEAM - Mediterranean Agronomic Institute of Bari, 70010, Valenzano, BA, Italy
| | - Roberto Capone
- Department of Organic Agriculture, CIHEAM - Mediterranean Agronomic Institute of Bari, 70010, Valenzano, BA, Italy
| | - Carlo Sabbà
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy
| | - Antonio Mazzocca
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy.
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Xi SY, Minuk GY. Role of traditional Chinese medicine in the management of patients with hepatocellular carcinoma. World J Hepatol 2018; 10:799-806. [PMID: 30533181 PMCID: PMC6280158 DOI: 10.4254/wjh.v10.i11.799] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 09/13/2018] [Accepted: 10/11/2018] [Indexed: 02/06/2023] Open
Abstract
Traditional Chinese Medicines (TCMs) have been employed for centuries in the treatment of patients with hepatocellular carcinoma (HCC). Previous reviews of this topic have focused on certain aspects of TCM treatment rather than an overall assessment of their value and mechanisms of action. Both the Chinese and English medical literatures were reviewed to identify where TCM might be of value in the treatment of HCC and the justification for such treatment. TCM treatment corrects the "internal disequilibriums" thought to be responsible for the development, growth, and spread of the tumor. It has also been used to manage symptoms associated with HCC and the adverse effects of chemo- and radiation-therapies. Recent research has documented the precise effects of TCM on tumor biology. There are also increasing efforts to identify which of the many components of TCM herbal remedies are primarily responsible for these beneficial effects. This review outlines the benefits of TCM treatment of HCC and the laboratory data describing their anti-tumor properties.
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Affiliation(s)
- Sheng-Yan Xi
- Department of Traditional Chinese Medicine, Medical College of Xiamen University, Cancer Research Center of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Gerald Yosel Minuk
- Section of Hepatology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
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Wang S, Long S, Wu W. Application of Traditional Chinese Medicines as Personalized Therapy in Human Cancers. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2018; 46:953-970. [DOI: 10.1142/s0192415x18500507] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Although lots of great achievements have been gained in the battle against cancer during the past decades, cancer is still the leading cause of death in the world including in developing countries such as China. Traditional Chinese medicine (TCM) is popular in Chinese and East Asian societies as well as some other Western countries and plays an active role in the modern healthcare system including patients with cancer, which may act as a potential effective strategy in treating human cancers. In this review, we aimed to introduce the mechanisms of TCM compound, as an option of individualized therapy, in treating cancer patients from the perspective of both Chinese and Western medicine. In the view of traditional Chinese medicine theory, individualized treatment for human cancers based on syndrome type benefits the cancer patients with personalized conditions. Balancing Qi, Xue, Yin and Yang, eliminating phlegm and removing dampness is how TCM compound functions on cancer patients. While in the view of Western medicine, inhibiting cancer cell growth and metastasis as well as improving immune status is how herbal compounds act on cancer patients. We also summarized the applications of TCM compound in human cancers, which will shed light on the clinical application of TCM compound on patients with cancer. TCM compound could be used as a complementary and alternative medicine (CAM) in human cancers. It could be applied in cancer patients with cancer-related fatigue (CRF). In addition, it is a good method for alleviating the side effects of both radiotherapy and chemotherapy. Therefore, TCM compound plays a critical role in treating patients with cancer, which has a promising strategy in the field of cancer management.
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Affiliation(s)
- Sumei Wang
- Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese, Medicine Guangzhou, Guangdong 510120, P. R. China
- The Postdoctoral Research Station, Guangzhou University of Chinese Medicine Guangzhou, Guangdong 510120, P. R. China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong 510120, P. R. China
| | - Shunqin Long
- Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese, Medicine Guangzhou, Guangdong 510120, P. R. China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong 510120, P. R. China
| | - Wanyin Wu
- Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese, Medicine Guangzhou, Guangdong 510120, P. R. China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong 510120, P. R. China
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Zhong P, Yang H, Lin S, Peng J, Lin J. A Traditional Chinese Medicine Herb Mixture Qingjie Fuzheng Granules Inhibits Hepatocellular Carcinoma Cells Growth by Inducing Apoptosis. J Evid Based Integr Med 2018; 23:2515690X18789632. [PMID: 30045633 PMCID: PMC6073831 DOI: 10.1177/2515690x18789632] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 05/27/2018] [Accepted: 06/26/2018] [Indexed: 12/12/2022] Open
Abstract
In this study, hepatocellular carcinoma (HCC) mouse xenograft model, MTT assay, colony formation, nuclear staining, and Annexin-V/PI staining assays were used to evaluate the effect of Qingjie Fuzheng granules (QFG) on cell proliferation and apoptosis of HCC cell in vivo and in vitro. Furthermore, Western blotting was performed to detect the expression of Fas, FasL, Bcl-2, Bax, and the activation of caspase-3/-8/-9. The results showed that QFG reduced tumor weight ( P < .05) but had no effect on body weight gain in HCC mice in vivo. QFG significantly reduced HCC cell viability and attenuated cell proliferation in a dose-dependent manner ( P < .05). QFG increased the expression of Fas, FasL, and Bax ( P < .05). QFG downregulated the expression of Bcl-2 and promoted the activation of caspase-8, -9, and -3 ( P < .05). These results suggested that QFG possessed anticancer effects, and the mechanisms of action may involve the death receptor pathway and mitochondrion-dependent pathway-mediated apoptosis.
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Affiliation(s)
- Pingping Zhong
- Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
- Both authors contributed equally
| | - Hong Yang
- Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
- Both authors contributed equally
| | - Shan Lin
- Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Jun Peng
- Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
| | - Jiumao Lin
- Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China
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Zhang Y, Liang Y, He C. Anticancer activities and mechanisms of heat-clearing and detoxicating traditional Chinese herbal medicine. Chin Med 2017; 12:20. [PMID: 28702078 PMCID: PMC5506596 DOI: 10.1186/s13020-017-0140-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 06/30/2017] [Indexed: 02/07/2023] Open
Abstract
In traditional Chinese medicine (TCM) theory, pathogenic heat and toxins, which are akin to the inflammatory factors, are the causes of cancer and could promote its virulent development. Therefore, heat-clearing and detoxicating (HCD) herbs are essential components of TCM formulas for cancer treatment. An increasing interest has been focused on the study of HCD herbs and accumulated evidences have shown that HCD herbs or HCD herbs-based formulas exhibited remarkable anticancer effects when used alone or combined with other therapeutic approaches. Some of the HCD herb-derived products have been tested in clinical trials. Studies revealed that extracts or pure compounds of the HCD herbs showed a broad anticancer spectrum against both solid and hematologic malignancies without significant toxic effects. Notably, some HCD herbs or formulas could strongly enhance the anticancer activities of chemo- or radio-therapy and alleviate their side effects. The anticancer activities of HCD herb exacts or the pure compounds were reported to be through multiple cellular or molecular mechanisms, such as induction of cancer cell apoptosis, differentiation and cell cycle arrest, inhibition of cancer cell growth, invasion and metastasis, and inhibition of tumor angiogenesis. In this review, we provide comprehensive analysis and summary of research progress and future prospects in this field to facilitate the further study and application of HCD herbs.
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Affiliation(s)
- Yulin Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078 China
| | - Yeer Liang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078 China
| | - Chengwei He
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, N22-7038, Avenida da Universidade, Taipa, Macao, 999078 China
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Liu Z, Liao L, Cao Z, Chen X, Du J. Synergisic effect of APRIL knockdown and Jiedu Xiaozheng Yin, a Chinese medicinal recipe, on the inhibition of hepatocellular carcinoma cell proliferation. Oncol Rep 2016; 37:754-760. [PMID: 28035399 PMCID: PMC5355738 DOI: 10.3892/or.2016.5339] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 09/01/2016] [Indexed: 12/24/2022] Open
Abstract
It is well documented that A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily, plays a crucial role in the occurrence and development of tumors. In the present study, we evaluated the synergistic effect of APRIL knockdown and Jiedu Xiaozheng Yin (JXY), a Traditional Chinese Medicinal recipe, on the inhibition of hepatocellular carcinoma (HCC) cell proliferation and elucidated the underlying mechanism. The results demonstrated that both APRIL knockdown using small interfering RNA (siRNA) and JXY treatment could trigger cell cycle arrest and cell apoptosis, and suppress HCC cell proliferation through an NF-κB-related pathway. Synergism was further demonstrated between APRIL knockdown and JXY treatment. In conclusion, these results indicate that APRIL is a target gene for HCC and combination of siRNA-APRIL and JXY application holds great promise as a novel approach for the treatment of APRIL-positive HCC.
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Affiliation(s)
- Zhizhen Liu
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Lianming Liao
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Zhiyun Cao
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Xuzheng Chen
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
| | - Jian Du
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
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Tan HY, San-Marina S, Wang N, Hong M, Li S, Li L, Cheung F, Wen XY, Feng Y. Preclinical Models for Investigation of Herbal Medicines in Liver Diseases: Update and Perspective. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2016; 2016:4750163. [PMID: 26941826 PMCID: PMC4749812 DOI: 10.1155/2016/4750163] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 12/23/2015] [Accepted: 12/30/2015] [Indexed: 02/07/2023]
Abstract
Liver disease results from a dynamic pathological process associated with cellular and genetic alterations, which may progress stepwise to liver dysfunction. Commonly, liver disease begins with hepatocyte injury, followed by persistent episodes of cellular regeneration, inflammation, and hepatocyte death that may ultimately lead to nonreversible liver failure. For centuries, herbal remedies have been used for a variety of liver diseases and recent studies have identified the active compounds that may interact with liver disease-associated targets. Further study on the herbal remedies may lead to the formulation of next generation medicines with hepatoprotective, antifibrotic, and anticancer properties. Still, the pharmacological actions of vast majority of herbal remedies remain unknown; thus, extensive preclinical studies are important. In this review, we summarize progress made over the last five years of the most commonly used preclinical models of liver diseases that are used to screen for curative herbal medicines for nonalcoholic fatty liver disease, liver fibrosis/cirrhosis, and liver. We also summarize the proposed mechanisms associated with the observed liver-protective, antifibrotic, and anticancer actions of several promising herbal medicines and discuss the challenges faced in this research field.
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Affiliation(s)
- Hor-Yue Tan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Serban San-Marina
- Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Ming Hong
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Lei Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Fan Cheung
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Xiao-Yan Wen
- Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
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