-desmethylangolensin inhibits the proliferation of human breast cancer MCF-7 cells by inducing apoptosis and promoting cell cycle arrest.

The aim of the present study was to investigate the anticancer effect of -desmethylangolensin (-DMA) by assessing cell proliferation, apoptosis and cell cycle distribution, as well as exploring the mechanisms underlying these effects in breast carcinoma MCF-7 cells. The cells were exposed to -DMA (5-200 μM) for 24, 48 and 72 h. The results revealed that cell proliferation was significantly inhibited in a dose-dependent manner following treatment for 48 and 72 h, but not after 24 h, and resulted in the significant induction of apoptosis and the promotion of cell cycle arrest at the G/S and G/M phases. To elucidate these effects of -DMA, the expression levels of cell cycle regulators were measured in the cells exposed to -DMA at 150 μM for 72 h. Of the G/S phase-related proteins, -DMA modulated the cyclin-dependent kinases (CDKs), with a decrease in CDK2 and CDK4 and an increase in CDK6, and downregulated cyclin D and E. With respect to the G/M-related proteins, -DMA caused a reduction in CDK1, together with a slight increase in cyclin A and B. In addition, -DMA downregulated p21 and p27, but not p16 and p15, and interacted with the CDK6-cyclin D and CDK1-cyclin B complexes. In conclusion, these results indicate for the first time that the regulation of the CDK4/6-cyclin D and CDK1-cyclin B complexes may participate in the anticancer activity pathway of -DMA in MCF-7 cells.