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Docosahexaenoic Acid (DHA) Induces P53-Dependent Growth Inhibition in Transformed Colon and Lung Cell Lines Expressing Wildtype P53

Abstract

Keith D. Kikawa, Noah T, Ahwah SM and Pardini RS

Supplementation with n-3 polyunsaturated fatty acids, both in dietary in vivo studies, as well as in vitro tissue culture models, has anti-proliferative effects on tumor cells. In the current study, the role of p53-dependent growth inhibition by docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is examined. Previous work has established that DHA is capable of growth inhibitory effects independent of p53 mutational status in colon carcinomas, however, one of the same studies showed an increase in the number of apoptotic cells (measured by Annexin V-FITC) only in the DHA- treated cells of the colon carcinoma with wildtype p53. To determine the potential role of p53 on the growth inhibition observed with DHA treatment of the human colon carcinomas COLO-205 (wildtype p53) and WiDr (mutant p53, His 237) and the human lung adenocarcinomas A549 (wildtype p53) and H441 (mutant p53, codon 158), p53-specific siRNA’s and a chemical inhibitor of p53, pifithrin-α, were employed in vitro . Significant increases in the number of DHA-treated cells by p53 siRNA or pifithrin-α addition were observed only in the COLO-205 and A549 cell lines expressing wildtype p53, and these correlated with a reduction in the percentage of apoptotic and necrotic cells. This data confirms a role for p53-dependent growth inhibition with DHA treatment.