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Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism

Authors' Affiliation: The Hormel Institute, University of Minnesota, Austin, MN

Requests for reprints: Margot P. Cleary, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912. Phone: 507-437-9655; Fax: 507-437-9606; E-mail: mpcleary{at}hi.umn.edu.

Eleostearic acid (-ESA) is a conjugated linolenic acid that makes up 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 -ESA on both estrogen receptor (ER)–negative MDA-MB-231 (MDA-wt) and ER-positive MDA-ER7 human breast cancer cells. We found that -ESA inhibited proliferation of both MDA-wt and MDA-ER7 cells, whereas conjugated linoleic acid had comparatively weak antiproliferative activity at 20 to 80 µmol/L concentrations. We also found that -ESA (40 µmol/L) treatment led to apoptosis in the range of 70% to 90% for both cell lines, whereas conjugated linoleic acid (40 µmol/L) resulted in only 5% to 10% apoptosis, similar to results for control untreated cells. Addition of -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, -ESA caused a G₂-M block in the cell cycle. We also investigated the potential for lipid peroxidation to play a role in the inhibitory action of -ESA. We found that when the breast cancer cells were treated with -ESA in the presence of the antioxidant -tocotrienol (20 µmol/L), the growth inhibition and apoptosis effects of -ESA were lost. An AMP-activated protein kinase inhibitor (Dorsomorphin) was also able to partially abrogate the effects of -ESA, whereas a caspase inhibitor (BOC-D-FMK) did not. These results illustrate that -ESA can block breast cancer cell proliferation and induce apoptosis through a mechanism that may be oxidation dependent.

Key Words: Breast cancer • long chain polyunsaturated fatty acid • Lipid peroxidation • Momordica charantia • Eleostearic Acid