Abstract
The rare flavone 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF) has been isolated from several plant species, and its cytotoxic activity has been reported against many types of cancer cells. In this study, PMF was purified from Glycomis ovoidea collected in Vietnam, and its antiproliferative effects and underlying mechanism of action were investigated against MCF-7 cells. PMF inhibited growth in MCF-7 > MCF-10A > MDA-MB-231 cells after 72 hr treatment, with IC50 values of 1.5, 1.9, and 8.6 μg/ml, respectively. Further experiments conducted with this compound in MCF-7 cells, showed the loss of mitochondrial membrane potential, reactive oxygen species overproduction, upregulation of BAX, cytochrome c, caspase-3 and PARP-1 and down-regulation of BCL-2 proteins as well as an increase in caspase-3/-7 activity, suggesting induction of the apoptotic intrinsic pathway. Furthermore, PMF increased cell cycle arrest in the G1 phase, which correlated with increments in the p53 and p21 levels. Additionally, MCF-7 cell migration was inhibited, which could be related to NF-κB p65 downregulation. Finally, PMF did not show toxicity in vivo in a zebrafish (Danio rerio) model. In conclusion, PMF induces cell death in MCF-7 cells through regulation of the BCL-2 protein family and may be proposed as a lead as a potential alternative for breast cancer therapy.