Anticancer Effects of Fucoxanthin in a PDX Model of Advanced Stage Pancreatic Cancer with Alteration of Several Multifunctional Molecules

Abstract

Pancreatic cancer (PC) is one of the most fatal cancers, and there is an urgent need to develop new anticancer agents with fewer side effects for the treatment of this condition. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissue from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates. Fucoxanthin (Fx) is a highly polar carotenoid contained in edible marine brown algae and possesses anticancer activity. However, there is a lack of data on the effects of Fx in PDX models. We investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with PC (PC-PDX) using comprehensive protein expression assay. Fx administration (0.3%Fx diet) ad libitum for 27 days significantly abrogated tumor development (0.4-fold) and induced tumor differentiation in PC-PDX mice, as compared to those in the control mice. Fx significantly upregulated the expression of non-glycanated DCN (2.4-fold), tended to increase the expressions of p-p38(Thr180/Tyr182) (1.6-fold) and pJNK(Thr183/Tyr185) (1.8-fold), significantly downregulated IGFBP2 (0.6-fold) and EpCAM (0.7-fold), and tended to decrease LCN2 (0.6-fold) levels in the tumors of the PC-PDX mice, as compared to those in the control mice. Some of the protein expression patterns were consistent with the in vitro experiments. That is, treatment of fucoxanthinol (FxOH), a prime metabolite derived from dietary Fx, enhanced non-glycanated DCN, p-p38(Thr180/Tyr182), and pJNK(Thr183/Tyr185) levels in human PC PANC-1 and BxPC-3 cells.These results suggested that Fx exerts anticancer and differentiation effects in a PC-PDX mice through alterations of some multifunctional molecules.

Keywords

• anticancer effect
• fucoxanthin
• patient-derived xenograft
• pancreatic cancer
• decorin
• heme oxygenase 1