Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer

• Published in: Pharmacological research Vol. 171; p. 105778
• Main Authors: Chen, Meng-Hua, Gu, Yue-Yu, Zhang, Anthony Lin, Sze, Daniel Man-yuen, Mo, Sui-Lin, May, Brian H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2021
• Subjects: Alkaloids - therapeutic use; Animals; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Cell-cycle; Colorectal cancer; Colorectal Neoplasms - drug therapy; Humans; Matrine; Multi-drug resistance; Phytotherapy; Quinolizines - therapeutic use; Signalling pathway; Sophora; miRNA-22; HMGB1; LRP; CXCL13; TAZ; Sophocarpine (Pubchem CID: 115269); HK2; Opa1; Cell-cycle; CNKI; mTOR; VEGFR; Apaf-1; MDR; INK4/ARF; Sophoridine (Pubchem CID: 165549); BCRP; P-gp; LATS1/2; MRPs; EMT; Matrine; CRC; CDKs; RCTs; MAPKAPK2; Smad; hTERT; MST1/2; NK; Cyto C; ABC; Multi-drug resistance; Colorectal cancer; FN; YAP; MIEF1; Drp1; CSA; GSK-3β; LDHA; MAFbx; CAFs; TAMs; Sophoraflavanone G (Pubchem CID: 9910234); Signalling pathway; Mfn2; TGF-β; MuRF-1; DMH; CKI; Fis1; GLUT1; HIF; Matrine (Pubchem CID: 91466); CI; VEGF; MMPs; Oxymatrine (Pubchem CID: 114850); RTKs; ECM; OCLN; STAT; APC; JAK; ATP; Apoptosis
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2021.105778

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. [Display omitted] •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.