Growth‐Inhibitory and Proapoptotic Effects of Alpha‐Linolenic Acid on Estrogen‐Positive Breast Cancer Cells

We tested the anticarcinogenic effect of alpha‐linolenic acid (ALA) as a single compound. To test the role of ALA in breast cancer cells (MCF‐7), we analyzed the antiproliferative pathway and the proapoptotic pathway. ALA exhibited growth inhibition on MCF‐7 cells dose‐dependently of ALA in 24, 48, and 72 h, without possible cytotoxicity per se. ALA enhanced the cell growth–inhibitory activity in a dose‐dependent manner. Second, the proapoptotic pathway showed a sub‐G 1 accumulation with concomitant upregulation of proapoptotic Bax expression, as well as a downregulation of antiapoptotic Bcl‐2 expression dose‐dependently, causing the Bcl‐2/Bax ratio to decrease by about 50%. Subsequent cytochrome c release and proteolytic activation of caspase‐3 followed by proteolytic cleavage of poly(ADP‐ribose) polymerase all suggest ensuing progression to apoptosis. This finding suggests that ALA alone might also be responsible for growth‐inhibitory and proapoptotic effects on estrogen‐positive breast cancer cells.