A Marine Carotenoid of Fucoxanthinol Accelerates the Growth of Human Pancreatic Cancer PANC-1 Cells

Abstract

Fucoxanthin and its metabolite fucoxanthinol (FxOH), highly polar xanthophylls, exert strong anticancer effects against many cancer cell types. However, the effects of Fx and FxOH on pancreatic cancer, a high mortality cancer, remain unclear. We herein investigated whether FxOH induces apoptosis in human pancreatic cancer cells. FxOH (5.0 μmol/L) significantly promoted the growth of human pancreatic cancer PANC-1 cells, but induced apoptosis in human colorectal cancer DLD-1 cells. A microarray-based gene analysis revealed that the gene sets of cell cycle, adhesion, PI3K/AKT, MAPK, NRF2, adipogenesis, TGF-β, STAT, and Wnt signals in PANC-1 cells were markedly altered by FxOH. A western blot analysis showed that FxOH up-regulated the expression of integrin β1 and PPARγ as well as the activation of pFAK(Tyr³⁹⁷), pPaxillin(Tyr³¹), and pAKT(Ser⁴⁷³) in PANC-1 cells, but exerted the opposite effects in DLD-1 cells. Moreover, the expression of FYN, a downstream target of integrin subunits, was up-regulated (7.4-fold by qPCR) in FxOH-treated PANC-1 cells. These results suggest that FxOH accelerates the growth of PANC-1 cells by up-regulating the expression of integrin β1, FAK, Paxillin, FYN, AKT, and PPARγ.

Author contribution statement

M. Terasaki conceived and designed the study and wrote the manuscript. M. Terasaki, T.O., S.T. and R.N. performed the experiments. A.K., H.K., J.H., Y.K., H.M., K.M., M. Takahashi and M. M. reviewed and edited the manuscript. All authors read and approved the manuscript and agree to be accountable for all aspects of the research and ensuring that the accuracy or integrity of any part of the work is appropriately investigated and resolved.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported in part by the Japan Society for the Promotion of Science KAKENHI (Grant Number 20K05879).