Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells

The sea squirt Halocynthia roretzi metabolizes fucoxanthin, and subsequently accumulates its derived carotenoids with characteristic structures. In the present study, we isolated halocynthiaxanthin and fucoxanthinol as carotenoids having antiproliferative activity from H. roretzi. Halocynthiaxanthin and fucoxanthinol inhibited the growth of HL-60 human leukemia cells in a dose- and time-dependent manner. Viability of HL-60 treated with 12.5 microM halocynthiaxanthin and fucoxanthinol was decreased by 12.1% and 5.7% of control after 48 h incubation, respectively. Furthermore, halocynthiaxanthin and fucoxanthinol induced apoptosis in HL-60 cells, MCF-7 human breast cancer cells, and Caco-2 human colon cancer cells. When HL-60 cells were incubated with 12.5 microM halocynthiaxanthin and fucoxanthinol for 48 h, relative DNA fragmentations were enhanced to 5- and 7-fold compared to that in control cells, respectively. The activities of apoptosis induction by halocynthiaxanthin and fucoxanthinol were higher than that of fucoxanthin which we have previously reported as a carotenoid possessing the ability to induce apoptosis. Fucoxanthinol exhibited the highest apoptosis-inducing activity among the three carotenoids. Furthermore, the expression levels of apoptosis-suppressing protein Bcl-2 were decreased in HL-60 cells treated with halocynthiaxanthin and fucoxanthinol. These results suggest that halocynthiaxanthin and fucoxanthinol exhibited potential antiproliferative effects via apoptosis induction in several cancer cell lines.