Docosahexaenoic Acid (DHA), a Primary Tumor Suppressive Omega-3 Fatty Acid, Inhibits Growth of Colorectal Cancer Independent of p53 Mutational Status

Abstract

Human colon carcinoma COLO 205, carrying wild type p53, grown subcutaneously in athymic mice was inhibited 80% by a high fat menhaden oil diet containing a mixture of omega-3 fatty acids compared to the low fat corn oil diet containing omega-6 fatty acids. Feeding a high fat diet of golden algae oil containing docosahexaenoic acid (DHA) as the sole long chain omega-3 fatty acid resulted in 93% growth inhibition. Similar findings were previously reported for WiDr colon carcinoma containing mutated p53 (His237). In vitro, 125 μM DHA inhibited COLO 205 growth by 81%, WiDr by 42%, while eicosapentaenoic acid (EPA) marginally inhibited growth of both lines by approximately 30%. DHA inhibited cell proliferation by 41% in WiDr but did not significantly inhibit proliferation in COLO 205. Cell cycle analysis revealed that DHA arrested cell cycle at Resting/Gap 1 (G0/G1 phase) in WiDr and at Gap 2/Mitosis (G2/M) phase in COLO 205. DHA induced apoptosis in COLO 205 but not in WiDr, and EPA did not induce apoptosis in either line. Taken together, these findings suggest DHA is the primary tumor suppressive ω-3 fatty acid in vivo and in vitro and inhibits cancer growth by p53 dependent and independent pathways, while the marginal inhibition by EPA is p53 independent.

Acknowledgments and Notes

Notes

^a Abbreviation is as follows: DHASCO, docosahexaenoic acid-rich single-cell oil.

^a Abbreviation is as follows: DHASCO, docosahexaenoic acid-rich single-cell oil.

^a Abbreviations are as follows: G1, Gap 1 phase; S, synthesis phase; G2, Gap 2 phase; LA, linoleic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid. Values represent relative percentages of cells in particular cell cycles; 20,000 gated cells were accounted for per sample. Values are mean standard error of the mean of the 3 independent experiments. Bold numbers indicate statistical significance compared to LA treated value.

^a Abbreviations are as follows: LA, linoleic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid. Values are mean standard error of the mean of the 3 separate experiments. Bold numbers indicate statistical significance as compared to LA treated samples.