Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer. (September 2021)

• Record Type: Journal Article
• Authors: Chen, Meng-Hua; Gu, Yue-Yu; Zhang, Anthony Lin; Sze, Daniel Man-yuen; Mo, Sui-Lin; May, Brian H.
• Is Part Of: Pharmacological research. Volume 171(2021)
• Publication Date: 2021-09
• Subjects: ABC Adenosine triphosphate (ATP)-binding cassette -- Apaf-1 Apoptosis protease activating factor-1 -- APC Adenomatous polyposis coli casein kinase 1 -- ATP Adenosine triphosphate -- BCRP Breast cancer resistance protein -- CAFs Cancer-associated fibroblasts -- CDKs Cyclin dependent kinases -- CI Combination index -- CKI Compound Kushen Injection -- CNKI China National Knowledge Infrastructure -- CRC Colorectal cancer -- CSA Cross-sectional area -- CXCL13 C-X-C motif ligand 13 -- Cyto C Cytochrome C -- DMH 1, 2-dimethylhydrazine dihydrochloride -- Drp1 Dynamin-related protein 1 -- ECM Extracellular matrix -- EMT Epithelial-mesenchymal transition -- Fis1 Mitochondrial fission 1 -- FN Fibronectin -- GLUT1 Glucose transporter 1 -- GSK-3β Glycogen synthase kinase 3β -- HIF Hypoxia inducible factor -- HK2 Hexokinase 2 -- HMGB1 High mobility group-B1 -- hTERT Human telomerase reverse transcriptase -- INK4/ARF Inhibitor of kinase 4/alternative reading frame -- JAK Janus kinases -- LATS1/2 Large tumour suppressor 1/2 -- LDHA Lactate dehydrogenase A -- LRP Lung resistance protein -- MAFbx Muscle atrophy F-Box -- MAPKAPK2 MAP kinase-activated protein kinase 2 -- MDR Multi-drug resistance -- Mfn2 Mitofusin 2 -- MIEF1 Mitochondrial elongation factor 1 -- miRNA-22 microRNA-22 -- MMPs Matrix metallopeptidases -- MRPs Multidrug resistance-associated proteins -- MST1/2 Mammalian Ste20-like kinases 1/2 -- mTOR mammalian target of rapamycin -- MuRF-1 Muscle ring-finger-1 -- NK Natural killer -- OCLN Occludin -- Opa1 Optic atrophy protein 1 -- P-gp P-glycoprotein -- RCTs Randomised controlled trials -- RTKs Receptor tyrosine kinases -- Smad Mothers against decapentaplegic homolog -- STAT Signal transducer and activator of transcription -- TAMs Tumour-associated macrophages -- TAZ WW domain containing transcription regulator 1 -- TGF-β Transforming growth factor beta -- VEGF Vascular endothelial growth factor -- VEGFR Vascular endothelial growth factor receptor -- YAP Yes association protein; Matrine (Pubchem CID: 91466) -- Oxymatrine (Pubchem CID: 114850) -- Sophoridine (Pubchem CID: 165549) -- Sophocarpine (Pubchem CID: 115269) -- Sophoraflavanone G (Pubchem CID: 9910234); Matrine -- Colorectal cancer -- Cell-cycle -- Apoptosis -- Signalling pathway -- Multi-drug resistance; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105778
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: The plant Sophora flavescens Ait. has been used in the clinical management of colorectal cancer (CRC). Its constituent compounds, notably the alkaloids matrine, oxymatrine, and sophoridine, have received considerable research attention in experimental models of CRC in vivo and in vitro. This review found that extracts of S. flavescens and/or its constituent compounds have been reported to inhibit CRC cell proliferation by inducing cell-cycle arrest at the G1 phase, inducing apoptosis via the intrinsic pathway, interfering in cancer metabolism, inhibiting metastasis and angiogenesis, regulating senescence and telomeres, regulating the tumour microenvironment and down-regulating cancer-related inflammation. In addition, matrine and oxymatrine reversed multi-drug resistance and enhanced the effects of chemotherapies. These anti-cancer effects were associated with regulation of several cellular signalling pathways including: MAPK/ERK, PI3K/AKT/mTOR, p38MAPK, NF-κB, Hippo/LATS2, TGF-β/Smad, JAK/STAT3, RhoA/ROC, and Wnt/ β-catenin pathways. These multiple actions in CRC suggest the alkaloids of S. flavescens may be therapeutic candidates for CRC management. Nevertheless, there remains considerable scope for future research into its flavonoid constituents, the effects of combinations of compounds, and the interaction between these compounds and anti-cancer drugs. In addition, more research is needed to investigate likely drug ligand-receptor interactions for each of the bioactive compounds. Graphical Abstract: ga1 Highlights: Suppressed CRC cell proliferation in vitro and in vivo . Induced CRC cell cycle arrest at G1 phase and induced apoptosis. Regulated CRC metabolism, metastasis, angiogenesis, senescence, tumour microenvironment, tumour-related inflammation and cachexia; and reversed multi-drug resistance. These anti-cancer effects were associated with regulation of several cellular signalling pathways including: MAPK/ERK, PI3K/AKT/mTOR, p38MAPK, NF-κB, Hippo/LATS2, TGF-β/Smad, JAK/STAT3, RhoA/ROC, and Wnt/ β-catenin pathways.