Eleostearic Acid inhibits breast cancer proliferation by means of an oxidation-dependent mechanism

• Published in: Cancer prevention research (Philadelphia, Pa.) Pa.), 2009-10, Vol.2 (10), p.879-886
• Main Authors: Grossmann, Michael E, Mizuno, Nancy K, Dammen, Michelle L, Schuster, Todd, Ray, Amitabha, Cleary, Margot P
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Breast Neoplasms - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Female; Humans; Linoleic Acid - pharmacology; Linolenic Acids - pharmacology; Membrane Potential, Mitochondrial - drug effects; Oxidation-Reduction - drug effects
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.capr-09-0088

Eleostearic acid (alpha-ESA) is a conjugated linolenic acid that makes up approximately 60% of Momordica charantia (bitter melon) seed oil. Prior work found that water extract from bitter melon was able to inhibit breast cancer. Here, we investigated effects of alpha-ESA on both estrogen receptor (ER)-negative MDA-MB-231 (MDA-wt) and ER-positive MDA-ERalpha7 human breast cancer cells. We found that alpha-ESA inhibited proliferation of both MDA-wt and MDA-ERalpha7 cells, whereas conjugated linoleic acid had comparatively weak antiproliferative activity at 20 to 80 micromol/L concentrations. We also found that alpha-ESA (40 micromol/L) treatment led to apoptosis in the range of 70% to 90% for both cell lines, whereas conjugated linoleic acid (40 micromol/L) resulted in only 5% to 10% apoptosis, similar to results for control untreated cells. Addition of alpha-ESA also caused loss of mitochondrial membrane potential and translocation of apoptosis-inducing factor as well as endonuclease G from the mitochondria to the nucleus. Additionally, alpha-ESA caused a G(2)-M block in the cell cycle. We also investigated the potential for lipid peroxidation to play a role in the inhibitory action of alpha-ESA. We found that when the breast cancer cells were treated with alpha-ESA in the presence of the antioxidant alpha-tocotrienol (20 micromol/L), the growth inhibition and apoptosis effects of alpha-ESA were lost. An AMP-activated protein kinase inhibitor (Dorsomorphin) was also able to partially abrogate the effects of alpha-ESA, whereas a caspase inhibitor (BOC-D-FMK) did not. These results illustrate that alpha-ESA can block breast cancer cell proliferation and induce apoptosis through a mechanism that may be oxidation dependent.