Antiadult T-cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol
Version of Record online: 16 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 123, Issue 11, pages 2702–2712, 1 December 2008
How to Cite
Ishikawa, C., Tafuku, S., Kadekaru, T., Sawada, S., Tomita, M., Okudaira, T., Nakazato, T., Toda, T., Uchihara, J.-N., Taira, N., Ohshiro, K., Yasumoto, T., Ohta, T. and Mori, N. (2008), Antiadult T-cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol. Int. J. Cancer, 123: 2702–2712. doi: 10.1002/ijc.23860
- Issue online: 24 SEP 2008
- Version of Record online: 16 SEP 2008
- Manuscript Accepted: 7 JUL 2008
- Manuscript Received: 8 MAY 2008
- Takeda Science Foundation
- Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science and Technology. Grant Number: 20012044
- Japan Society for the Promotion of Science. Grant Number: 19591123
Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by human T-cell leukemia virus type 1 (HTLV-1) infection and remains incurable. Carotenoids are a family of natural pigments and have several biological functions. Among carotenoids, fucoxanthin is known to have antitumorigenic activity, but the precise mechanism of action is not elucidated. We evaluated the anti-ATL effects of fucoxanthin and its metabolite, fucoxanthinol. Both carotenoids inhibited cell viability of HTLV-1-infected T-cell lines and ATL cells, and fucoxanthinol was approximately twice more potent than fucoxanthin. In contrast, other carotenoids, β-carotene and astaxanthin, had mild inhibitory effects on HTLV-1-infected T-cell lines. Importantly, uninfected cell lines and normal peripheral blood mononuclear cells were resistant to fucoxanthin and fucoxanthinol. Both carotenoids induced cell cycle arrest during G1 phase by reducing the expression of cyclin D1, cyclin D2, CDK4 and CDK6, and inducing the expression of GADD45α, and induced apoptosis by reducing the expression of Bcl-2, XIAP, cIAP2 and survivin. The induced apoptosis was associated with activation of caspase-3, -8 and -9. Fucoxanthin and fucoxanthinol also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of nuclear factor-κB and activator protein-1. Mice with severe combined immunodeficiency harboring tumors induced by inoculation of HTLV-1-infected T cells responded to treatment with fucoxanthinol with suppression of tumor growth, showed extensive tissue distribution of fucoxanthinol, and the presence of therapeutically effective serum concentrations of fucoxanthinol. Our preclinical data suggest that fucoxanthin and fucoxanthinol could be potentially useful therapeutic agents for patients with ATL. © 2008 Wiley-Liss, Inc.