Conjugated Docosahexaenoic Acid Is a Potent Inducer of Cell Cycle Arrest and Apoptosis and Inhibits Growth of Colo 201 Human Colon Cancer Cells

Abstract

Abstract: The effect of conjugated docosahexaenoic acid (CDHA) on the inhibition of colon cancer cell growth was examined in the colo 201 human colon cancer cell line, and the effect was compared with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). CDHA was a more potent tumor cell growth inhibitor than DHA and EPA by colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay (IC₅₀ for 72 h: 31.6 μM, 46.8 μM, and 56.6 μM, respectively). CDHA inhibited cell cycle progression, due to accumulation of cells in G1 phase, which involved increased p21^Cip1/Waf1 and decreased cyclin D1, cyclin E, and proliferating cell nuclear antigen expression; the p53 and cyclin A levels were unchanged. Induction of apoptosis was confirmed by the appearance of sub-G1 populations, and apoptosis cascade involved upregulation of the apoptosis-enhancing proteins (Bak and Bcl-ϰ_S) and downregulation of the apoptosis-suppressing proteins (Bcl-ϰ_L and Bcl-2). CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins, similar to the effects of DHA. CDHA at a dietary dose of 1.0% significantly inhibited growth of colo 201 cells transplanted in nude mice.