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

Area of Science:

• Marine natural products
• Cancer research
• Cell biology

Background:

• Fucoxanthin (Fx) and its metabolite fucoxanthinol (FxOH) exhibit anti-cancer properties.
• The precise mechanisms underlying Fx and FxOH's anti-cancer effects, particularly in colorectal cancer (CRC), remain largely unelucidated.
• Recent studies suggest FxOH can induce anoikis-like cell death in CRC cells.

Purpose of the Study:

• To establish molecular hallmarks for anoikis in vitro.
• To investigate the chemopreventive effects of Fx in a colorectal cancer model.
• To confirm if Fx ingestion induces the identified anoikis hallmarks in vivo.

Main Methods:

• Developed in vitro molecular hallmarks for anoikis using DLD-1 CRC cells treated with FxOH.
• Utilized an azoxymethane/dextran sodium sulfate (DSS) mouse model to induce colorectal carcinogenesis.
• Administered Fx to mice and analyzed colonic tissues for polyp formation and the expression of anoikis markers (integrin β1, p-FAK, p-Paxillin, cleaved caspase-3).

Main Results:

• Established that integrin β1^low/-, p-FAK(Tyr³⁹⁷)^low/-, p-Paxillin(Tyr³¹)^low/-, and cleaved caspase-3^high are potential molecular hallmarks of anoikis.
• Fx administration (30 mg/kg) significantly reduced polyp number and size in the CRC model.
• Fx treatment markedly increased the prevalence of cells exhibiting the anoikis hallmarks in colonic crypts (2.2- to 5.2-fold increase).

Conclusions:

• Fx demonstrates chemopreventive potential against colorectal cancer.
• The anti-cancer mechanism of Fx involves the induction of anoikis-like cells.
• The identified molecular hallmarks are valuable for assessing Fx's therapeutic effects.