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The induction of apoptosis in pre-malignant keratinocytes by polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is inhibited by albumin.

Toxicol Lett. 2013 Feb 4;

Authors: Nikolakopoulou Z, Shaikh MH, Dehlawi H, Michael-Titus AT, Parkinson EK


The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. At the 10% vol/vol foetal bovine serum (FBS) medium, limited growth inhibition (3%-20% for 50μM DHA and EPA respectively) and negligible apoptosis were observed with PUFA use. However, at 3% vol/vol FBS medium, 30-50μM of PUFA caused impressive levels of growth inhibition (82%-83% for 50μM DHA and EPA respectively) and increase of apoptosis (8%-19% increase in 72h). None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-α-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1-0.3% w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses.

PMID: 23391486 [PubMed - as supplied by publisher]