COMBINATION OF BERBERINE AND MATRINE AFFECTS APOPTOSIS AND CELLCYCLE IN HUMAN CERVICAL CANCER CELLS
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Cervical cancer is the fourth leading cause of malignancy-related mortality in women worldwide, and effective advanced-stage therapies are urgently required. Berberine is a quaternary ammonium compound extracted from traditional Chinese medicinal herbs, including Phellodendron spp., with antibacterial and antitumor activities. Matrine, the main active ingredient of Sophora flavescens rhizomes, has not only traditionally described health effects but is also widely used for its anticancer, anti-inflammatory, immunoregulatory, antiviral, and hepatoprotective effects. We investigated the antitumor activities of berberine and matrine against human cervical cancer HeLa and SiHa cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, along with flow cytometry and western blotting analyses, to assess the effect of the compounds on the cellular status and apoptosis- and cell cycle-related proteins. The 24 h half-maximal inhibitory concentrations (IC50) of berberine and matrine were 123.633 ± 4.278 µmol/L and 9.625 ± 0.245 mmol/L against HeLa cells and 105.067 ± 3.745 µmol/L and 8.50 ± 0.23 mmol/L against SiHa cells, respectively. Berberine plus matrine inhibited cancer cell growth and caused cell cycle arrest. We observed an increased stimulation of apoptosis, which was likely mediated by enhanced levels of caspase-3, caspase-9, and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), as well as decreased Bcl-2 protein expression. Cell cycle arrest in the G1 phase was probably mediated by p21 upregulation and cyclin-dependent kinase (Cdk)-4, Cdk-6, and cyclin D1 suppression. Combination treatment with berberine and matrine effectively inhibited human cervical cancer cell proliferation, most likely by stimulating apoptosis and inducing cell cycle arrest.
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