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.
Kim
Ji-Yoon
JY
Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea.
Park
Han Deuk
HD
Park
Eunju
E
Chon
Jeong-Woo
JW
Park
Yoo Kyoung
YK
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D017962:alpha-Linolenic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D051028:bcl-2-Associated X Protein; D017962:alpha-Linolenic Acid; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3