Anticancer effects of marine carotenoids, fucoxanthin and its deacetylated product, fucoxanthinol, on osteosarcoma.
Anticancer effects of marine carotenoids, fucoxanthin and its deacetylated product, fucoxanthinol, on osteosarcoma.
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DOI：
10.3892/ijo.2013.2019
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发表时间：
2013-10
影响因子：
5.2
通讯作者：
Takayoshi Rokkaku;Ryuichiro Kimura;Chie Ishikawa;T. Yasumoto;M. Senba;F. Kanaya;N. Mori
中科院分区：
文献类型：
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作者：
Takayoshi Rokkaku;Ryuichiro Kimura;Chie Ishikawa;T. Yasumoto;M. Senba;F. Kanaya;N. Mori
骨肉瘤患者的生存取决于对复发和转移病变的预防或治疗。因此，需要新的化疗药物来更有效地治疗和预防这种疾病。类胡萝卜素是一种天然色素，具有多种生物学功能。我们评价了几种类胡萝卜素的抗骨肉瘤特性。在类胡萝卜素中，岩藻黄质及其代谢物岩藻黄质醇对骨肉瘤细胞系的细胞活力有抑制作用。Fucoxanteol通过降低细胞周期蛋白依赖性激酶4、细胞周期蛋白依赖性蛋白6和细胞周期蛋白E的表达，诱导细胞周期停滞于G1期，并通过抑制Survivin、XIAP、Bcl2和Bclxl的表达诱导细胞凋亡。细胞凋亡与caspase-3、-8和-9的激活有关。此外，岩藻糖醇还可抑制磷酸肌醇依赖的K1和AKT的磷酸化以及下游糖原合成酶K3β的磷酸化，从而下调β-连环蛋白的表达。岩藻糖醇可抑制骨肉瘤细胞的迁移和侵袭。它还降低了基质金属蛋白酶-1的表达和激活蛋白-1的信号。用岩藻黄质接种小鼠骨肉瘤细胞可抑制小鼠骨肉瘤的发展。岩藻黄质和岩藻糖醇抑制骨肉瘤细胞的生长、迁移和侵袭，并诱导骨肉瘤细胞凋亡，至少部分是通过抑制Akt和激活蛋白-1途径实现的。我们的发现为这些新药治疗骨肉瘤的临床评估提供了理论依据。
Survival of osteosarcoma patients hinges on prevention or treatment of recurrent and metastatic lesions. Therefore, novel chemotherapeutics for more effective treatment and prevention of this disease are required. Carotenoids are natural pigments and exhibit various biological functions. We evaluated the anti-osteosarcoma properties of several carotenoids. Among carotenoids, fucoxanthin and its metabolite fucoxanthinol, inhibited the cell viability of osteosarcoma cell lines. Fucoxanthinol induced G1 cell cycle arrest by reducing the expression of cyclin-dependent kinase 4, cyclin-dependent kinase 6 and cyclin E and apoptosis by reducing the expression of survivin, XIAP, Bcl-2 and Bcl-xL. Apoptosis was associated with activation of caspases-3, -8 and -9. In addition, fucoxanthinol inhibited the phosphorylation of phosphoinositide-dependent kinase 1 and Akt and the downstream glycogen synthase kinase 3β, resulting in downregulation of β-catenin. Fucoxanthinol inhibited the cell migration and invasion of osteosarcoma cells. It also reduced matrix metalloproteinase-1 expression and the activator protein-1 signal. Treatment of mice inoculated with osteosarcoma cells with fucoxanthin inhibited the development of osteosarcoma in mice. Fucoxanthin and fucoxanthinol inhibit cell growth, migration and invasion and induce apoptosis of osteosarcoma cells at least in part by inhibiting Akt and activator protein-1 pathways. Our findings provide a rationale for clinical evaluation of these novel agents in osteosarcoma.