Abstract
Breast
cancer is currently the leading cause of cancer-related deaths among
women globally. Notably, medicinal plant extracts may be a potential
source for treatments of breast cancer.
Vernonia amygdalina
(VA) is a woody shrub reported to have not only diverse therapeutic
effects but also anti-cancer properties. However, current research about
the mechanisms of the anti-cancer potential of VA has been limited.
This study aimed to investigate the mechanisms of action of VA that
underlie its anti-cancer effects in human breast cancer cell lines
(MCF-7 and MDA-MB-231 cells). Results from MTT assay revealed that VA
inhibits the proliferation of MCF-7 and MDA-MB-231, in a time- and
dose-dependent manner. The underlying mechanism of this growth
inhibition involved the stimulation of cell-type specific G1/S phase
cell cycle arrest in only MCF-7 cells, and not in MDA-MB-231 cells.
While the growth arrest was associated with increased levels of p53 and
p21, and a concomitant decrease in the levels of cyclin D1 and cyclin E,
it was shown that VA causes cell cycle arrest through a p53-independent
pathway as tested by the wild type p53 inhibitor, pifithrin-α.
Furthermore, this study revealed that VA induces apoptosis in the two
cell lines, as indicated by the increase in Annexin V-positive cells and
sub-G1 population, and that this VA-induced apoptosis occurred through
both extrinsic and intrinsic apoptotic pathways. The apoptosis in MCF-7
cells was also likely to be caspase-dependent and not p53
transcriptional-dependent. Given that approximately 70% of diagnosed
breast cancers express ER-α, a crucial finding was that VA inhibits the
expression of ER-α and its downstream player, Akt, highlighting the
potential clinical significance of VA. Moreover, VA exhibits synergism
when combined with doxorubicin, suggesting that it can complement
current chemotherapy. Overall, this study demonstrates the potential
applications of VA as an anti-cancer drug for breast cancer treatment.
