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 muM 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 omega-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.

Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds

“…Studies with fish oil, which contains eicosapentaenoic acid and docosahexaenoic acid (DHA) showed that it has anti-inflammatory and anti-cancer properties. DHA treatment inhibits colon cancer growth through inducing apoptosis and cell-cycle arrest [68]. DHA also suppressed arachidonic acid-induced cell proliferation, PGE 2 production, and COX-2 expression in human colon carcinoma cells [69].…”

Fatty acids as potential adjunctive colorectal chemotherapeutic agents

“…LCFA include palmitic acid (C16:0) (PMA), α-linolenic acid (18:3) (ω-3), conjugated linoleic acid (18:2) (ω-6) (CLA), linoleic acid (18:2) (ω-6) (LA), oleic acid (18:1) (ω-9) (OA), arachidonic acid (22:4) (ω-6) (AA), eicosapentaenoic acid (EPA) (20:5) (ω-3) and docosahexaenoic acid (DHA) (22:6) (ω-3). 38,[84][85][86] LCFA have demonstrated in-vitro anti-neoplastic properties in breast, prostate and CRC cell lines by cellular differentiation, cell cycle arrest and increasing oxidative stress, all leading to the induction of apoptosis. 30,87 Induction of apoptosis by LCFA in colorectal cancer cell lines.…”

“…These investigators concluded that DHA exerted antitumorigenic activities dependent on p53 status, whereas EPA actions were p53 independent. 85 The related cell lines SW480 and SW620 demonstrated time-dependent cell cycle arrest when incubated with DHA, indicating that induction of cell death could be optimised through timing of administration of adjunctive therapy.…”

Induction of Apoptosis by the Medium-Chain Length Fatty Acid Lauric Acid in Colon Cancer Cells due to Induction of Oxidative Stress

“…LCFA have also demonstrated apoptotic properties, with palmitic acid, α-linoleic acid, CLA, and DHA inducing apoptosis in a range of CRC cell lines, including Caco-2, HTC-116, and COLO 205 cell lines. This is believed to be a consequence of lipid peroxidation, modification of cell cycle phases, induction of p21, an increase in the proapoptotic gene NAG-1, and altered P13 kinase and p38 MAPK pathways [13,14,15,16,17]. …”