Growth inhibition and apoptotic effect of alpha-eleostearic acid on human breast cancer cells

Abstract

Alpha-eleostearic acid (α-ESA) is a natural and biologically active compound which possesses potent antioxidant and anti-tumor activity. The purpose of this study was to confirm the anticancer activity of α-ESA against human breast cancer cells and to further elucidate its mechanism of activity. Human breast cancer cells and normal liver cells were used for in-vitro tests of the anticancer activity of α-ESA, including cytotoxicity, colony formation inhibition, EdU incorporation, AO/EB staining of apoptotic cells, cell cycle distribution through flow cytometry, and PPARγ, p21, Bax, p53, and caspase-3 mRNA expressions through RT-PCR. After α-ESA treatment, the proliferation, colony formation, and EdU labeling indices of cancer cells decreased (p < 0.05), while the AO/EB-stained apoptotic cells increased (p < 0.05). By FCM analysis, the apoptotic indices increased (p < 0.01), and the cell population decreased in S phase (p < 0.01) and increased in G(2)/M phase (p < 0.05) in α-ESA treated cancer cells. RT-RCR showed that α-ESA significantly increased the expression levels of PPARγ, p21, Bax, p53, and caspase-3 mRNA. The findings in these studies suggested that α-ESA exhibited a potential cytotoxicity and apoptosis induction effect on human breast cancer cells, with little effect on normal cells at certain concentrations. The mechanism for such effects might be associated with the inhibition of DNA synthesis, induction of apoptosis, and cell cycle arrest of cancer cells through up-regulation of PPARγ, p21, Bax, p53, and caspase-3 expressions.