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.
Highlights
As the most common cancer among women around the globe, breast cancer is currently the leading cause of cancer-related deaths in the world [1,2]
As a basis for further characterization of Vernonia amygdalina (VA)-induced cellular response in MCF-7 and MDA-MB-231, the ethanolic extract of VA was first examined for its ability to inhibit the proliferation of the two cell lines using MTT assay
At the highest dose of VA (200 mg/ml), cell viability of MCF-7 cells appeared to be independent of time
Summary
As the most common cancer among women around the globe, breast cancer is currently the leading cause of cancer-related deaths in the world [1,2]. The search for new and effective drugs to treat breast cancer is of central importance, given the drawbacks involved in current treatment methods that compromise their effectiveness. In this search for new drugs, medicinal plant extracts may be a potential source for alternative novel treatments of breast cancer. There has been growing interest in one particular plant as a source for anti-cancer drugs due to its diverse medicinal uses in traditional folk medicines. Owing to the lack of documentation of this plant, different local names have been used in various countries, such as Etidod or Ewuro in Nigeria, South
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