Neoxanthin and fucoxanthin induce apoptosis in PC-3 human prostate cancer cells

Abstract 

Neoxanthin and fucoxanthin, which have the characteristic structure of 5,6-monoepoxide and an allenic bond, were previously found to reduce the viability of human prostate cancer cells most intensively among 15 dietary carotenoids tested. In the present study, the induction of apoptosis in PC-3 cells by these two carotenoids was characterized by morphological changes, DNA fragmentation, an increased percentage of hypodiploid cells, and cleavages of caspase-3 and PARP. The ratio of apoptotic cells reached more than 30% after treatment for 48h with 20μM carotenoids. They reduced the expression of Bax and Bcl-2 proteins, but not Bcl-X_L. Fucoxanthin accumulated in the cells at the same level as neoxanthin. Moreover, fucoxanthinol, a deacetylated product of fucoxanthin, formed in the cells treated with fucoxanthin and reached a level comparable to that of fucoxanthin after incubation for 24h. Treatment by fucoxanthinol alone also induced apoptosis in PC-3 cells. Thus, neoxanthin and fucoxanthin treatments were found to induce apoptosis through caspase-3 activation in PC-3 human prostate cancer cells.

Keywords: Neoxanthin, Fucoxanthin, Fucoxanthinol, Carotenoid, Apoptosis, Prostate cancer cells

Abbreviations: DCDDF-DA, diacetoxymethyl 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate, DMEM, Dulbecco's Modified Eagle's medium, FACS, fluorescence-activated cell sorting, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, PARP, poly (ADP-ribose) polymerase, ROS, reactive oxygen species, THF, tetrahydrofuran, TUNEL, TdT-mediated dUTP nick end labeling