Fucoxanthin potentiates anoikis in colon mucosa and prevents carcinogenesis in AOM/DSS model mice

Abstract

Fucoxanthin (Fx) and its biotransformed fucoxanthinol (FxOH) present strong anti-cancer effects in vitro and in vivo, however, the underlying mechanisms are not well known. We recently demonstrated that FxOH could induce anoikis-like cells in human colorectal cancer (CRC) cells. Thus, we developed molecular hallmarks for anoikis in vitro, and to confirm induction of such molecular hallmarks in an azoxymethane/ dextran sodium sulfate carcinogenic model by Fx ingestion. During the process of anoikis by FxOH (2.5 μmol/l) in DLD-1 cells, the cells show the characteristics of integrin β1^low/-, p-FAK(Tyr³⁹⁷)^low/- or p-Paxillin(Tyr³¹)^low/- cells with cleaved caspase-3^high, which may be useful as molecular hallmarks. Fx administration (30 mg/kg body weight) significantly suppressed the number and size of polyps compared with untreated control mice. In addition, the incidence and multiplicity of colonic lesions tended to reduce. Moreover, cells showing integrin β1^low/-, p-FAK(Tyr³⁹⁷)^low/- and p-Paxillin(Tyr³¹)^low/- with cleaved caspase-3^high in colonic crypts were significantly increased 2.2-, 4.8- and 5.2-fold by Fx administration compared with untreated control mice, respectively. Our results suggest that Fx showed a chemopreventive effect in the carcinogenic models through anoikis-like cells induction.

Keywords: Anoikis; Cancer chemoprevention; Carotenoid; Colorectal cancer; Fucoxanthin.