Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells

Background: Bioactive marine molecules have recently received considerable attention for their nutraceutical characteristics. Considering the ever-increasing demand of nutraceuticals for anti-cancer therapy, we investigated the apoptosis-inducing effects of marine carotenoids, including siphonaxanthin, on human leukemia (HL-60) cells. Methods: Apoptotic effects were evaluated by cell viability assay. TUNEL assay, and caspase-3 activity. The expression of apoptosis-inducing death receptor-5 (DR5). Bcl-2 and Bax were assayed by Western blot analysis, and mRNA expression of GADD45 alpha was assayed by quantitative RT-PCR analysis. Results: Siphonaxanthin potently inhibited the viability of HL-60 cells compared with the other carotenoids evaluated. In comparison with fucoxanthin, siphonaxanthin at a concentration of 20 mu M markedly reduced cell viability (p < 0.05) as early as within 6 h of treatment. The effective apoptotic activity of siphonaxanthin was observed by increases in TUNEL-positive cells, and by increased chromatin condensation in HL-60 cells. This induction of apoptosis was associated with the decreased expression of BcI-2, and the subsequently increased activation of caspase-3. In addition, siphonaxanthin up-regulated the expression of GADD45 alpha and DR5. Conclusions: These data suggest that the dietary carotenoid siphonaxanthin could be potentially useful as a chemopreventive and/or chemotherapeutic agent. General significance: Our findings demonstrate for the first time the novel functional property of siphonaxanthin as a potent inducer of apoptosis in HL-60 cells. (C) 2011 Elsevier B.V. All rights reserved.