Anticancer effects of sanguinarine in triple-negative breast cancer cells via apoptosis induction and cell cycle arrest

Abstract Patients with triple-negative breast cancer (TNBC) are typically treated with non-targeted chemotherapeutic agents, and the late disease stages are known to be resistant to chemotherapy. Therefore, it is necessary to develop novel therapeutic agents that are safer and more effective for enhancing the outcomes of chemotherapeutic agents. The natural alkaloid sanguinarine (SANG) is a quaternary benzophenanthridine alkaloid that has demonstrated synergistic therapeutic effects when combined with various chemotherapeutic drugs. SANG can also induce cell cycle arrest and trigger apoptosis in various cancer cells. Therefore, in this study, we investigated the molecular mechanism underlying SANG activity in MDA-MB-231 and MDA-MB-468 cells, as two genetically different models of TNBC. SANG decreased the viability of both cell lines, but MDA-MB-468 cells were more sensitive to SANG than MDA-MB-231 cells. SANG affected cell cycle progression in both cell lines. Further, S-phase cell cycle arrest-mediated apoptosis was found to be the primary contributor to cell growth inhibition in MDA-MB-231 cells. SANG-treated TNBC cells showed significantly upregulated mRNA expression of 18 genes associated with apoptosis, including eight members of the TNF receptor superfamily (TNFRSF), three members of the BCL2 family, and two members of the caspase (CASP) family in MDA-MB-468 cells; in MDA-MB-231 cells, two members of the TNF superfamily and four members of the BCL2 family were affected. In conclusion, these results indicate that SANG shows markedly different anticancer effects and apoptosis-related gene expression changes in the two cell lines. Thus, SANG demonstrates potent anticancer effects in TNBC cell lines, suggesting its potential as a single or adjunct therapeutic agent against TNBC.