Incorporation of branched-chain fatty acid into cellular lipids and caspase-independent apoptosis in human breast cancer cell line, SKBR-3

BACKGROUND: 13-Methyltetradecanoic acid (13-MTD), an iso-C15 branched- chain saturated fatty acid, has been shown to induce apoptotic cell death of numerous human cancer cells. However, the mechanism for the induction of apoptosis has not been fully understood. This study described the incorporation of 13-MTD into cellular lipid of SKBR-3 breast cancer cells and apoptosis related event to gain more insight into the mechanism action of this fatty acid. RESULTS: Treatment of SKBR-3 cells with 13-MTD lowered the cell viability and induced apoptosis. Proportion of 13-MTD in the glycerolipids increased to saturation level within 6 hours. Triacylglycerol contained 13-MTD in higher concentration than phospholipid with positional preference to sn-2. 13-MTD caused no changes in the caspase activity and its gene expression. Furthermore, addition of caspase-inhibitor to culture medium did not prevent the cells from the cytotoxicity of 13-MTD. No-increase in the cellular calcium level was also noted with 13-MTD treatment. However, 13-MTD disrupted the mitochondrial integrity in 4 hours, and increased the nuclear translocation of apoptosis inducing factor. CONCLUSION: These results showed that 13-MTD disrupted the mitochondrial integrity, and induced apoptosis via caspase-independent death pathway.