A Mixture of trans, trans Conjugated Linoleic Acid Induces Apoptosis in MCF-7 Human Breast Cancer Cells with Reciprocal Expression of Bax and Bcl-2

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Abstract
The growth inhibitory effect of a mixture of trans,trans conjugated linoleic acid isomers (t,t CLA) was investigated in a human breast cancer cell line, MCF-7, with references to c9,t11 CLA, t10,c12 CLA, and linoleic acid. The t,t CLA treatment effectively induced a cytotoxic effect in a time-dependent (0−6 days) and concentration-dependent (0−40 µM) manner, as compared to the reference and control treatments. The apoptotic parameters were measured on cells treated with 40 µM t,t CLA for 4 days. The occurrence of the characteristic morphological changes and DNA fragmentation confirmed apoptosis. The t,t CLA treatment led to an increase in the level of p53 tumor suppressor protein and Bax protein, but suppressed the expression of Bcl-2 protein. In addition, cytochrome c was released from the mitochondria into the cytosol, and the activation of caspase-3 led to the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, the composition of the linoleic and arachidonic acids was decreased in cellular membranes. These findings suggest that incorporation of t,t CLA in the membrane induces a mitochondria-mediated apoptosis that can enhance the antiproliferative effect of t,t CLA in MCF-7 cells.

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