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Achyrocline satureioides compounds, achyrobichalcone and 3‐O‐methylquercetin, induce mitochondrial dysfunction and apoptosis in human breast cancer cell lines

Natural products are a valuable source of new molecules and are important for drug discovery. Many chemotherapeutics currently in clinical use were originated from natural sources and are effective cytotoxic agents. In this study, we investigated the cytotoxic and pro‐apoptotic effects of achyrobichalcone (ACB) and 3‐O‐methylquercetin (3OMQ), two novel compounds isolated from the Achyrocline satureioides plant. Because extracts from this plant have been shown to have anticancer activity in vitro, we evaluated ACB and 3OMQ using a human breast cancer cell line, MDA‐MB‐231, and a nontumorigenic human breast epithelial cell line, MCF‐12A. We found that ACB demonstrates cytotoxic effects on MDA‐MB‐231 cells, but not MCF‐12A cells. 3OMQ also demonstrated cytotoxic effects on MDA‐MB‐231 cells, but with lower selectivity compared to treated MCF‐12A cells. Cell death by both compounds was associated with caspase‐9 and caspase‐3/7 activation. Using high‐resolution respirometry, we found that ACB and 3OMQ were able to cause acute mitochondrial dysfunction in MDA‐MB‐231‐treated cells. These results suggest that apoptosis in MDA‐MB‐231 cells is induced through the activation of the mitochondrial‐dependent pathway. Collectively, these findings suggest that ACB is a strong candidate for further anticancer in vivo tests.