Ganesan Ponesakki, Noda Kenji, Manabe Yuki, Ohkubo Takeshi, Tanaka Yukihisa, Maoka Takashi, Sugawara Tatsuya, Hirata Takashi
Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Biochim Biophys Acta. 2011 May;1810(5):497-503. doi: 10.1016/j.bbagen.2011.02.008. Epub 2011 Mar 1.
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.
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 GADD45α was assayed by quantitative RT-PCR analysis.
Siphonaxanthin potently inhibited the viability of HL-60 cells compared with the other carotenoids evaluated. In comparison with fucoxanthin, siphonaxanthin at a concentration of 20μM markedly reduced cell viability (p<0.05) as early as within 6h 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 Bcl-2, and the subsequently increased activation of caspase-3. In addition, siphonaxanthin up-regulated the expression of GADD45α and DR5.
These data suggest that the dietary carotenoid siphonaxanthin could be potentially useful as a chemo-preventive and/or chemotherapeutic agent.
Our findings demonstrate for the first time the novel functional property of siphonaxanthin as a potent inducer of apoptosis in HL-60 cells.
生物活性海洋分子因其营养保健特性最近受到了广泛关注。鉴于营养保健品在抗癌治疗方面的需求不断增加，我们研究了包括虹吸叶黄素在内的海洋类胡萝卜素对人白血病（HL - 60）细胞的凋亡诱导作用。
通过细胞活力测定、TUNEL测定和半胱天冬酶 - 3活性评估凋亡效应。通过蛋白质免疫印迹分析检测凋亡诱导死亡受体 - 5（DR5）、Bcl - 2和Bax的表达，通过定量RT - PCR分析检测GADD45α的mRNA表达。
与其他评估的类胡萝卜素相比，虹吸叶黄素能有效抑制HL - 60细胞的活力。与岩藻黄质相比，浓度为20μM的虹吸叶黄素早在处理6小时内就显著降低了细胞活力（p<0.05）。通过TUNEL阳性细胞增加以及HL - 60细胞中染色质浓缩增加，观察到虹吸叶黄素有效的凋亡活性。这种凋亡诱导与Bcl - 2表达降低以及随后半胱天冬酶 - 3的激活增加有关。此外，虹吸叶黄素上调了GADD45α和DR5的表达。
这些数据表明，膳食类胡萝卜素虹吸叶黄素可能具有潜在的化学预防和/或化疗药物的作用。
我们的研究结果首次证明了虹吸叶黄素作为HL - 60细胞凋亡强效诱导剂的新功能特性。
