Growth inhibition of human hepatic carcinoma HepG2 cells by fucoxanthin is associated with down-regulation of cyclin D
Growth inhibition of human hepatic carcinoma HepG2 cells by fucoxanthin is associated with down-regulation of cyclin D
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DOI：
10.1016/j.bbagen.2008.01.003
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发表时间：
2008-04-01
影响因子：
3
通讯作者：
Kanazawa, Kazuki
中科院分区：
文献类型：
--
作者：
Das, Swadesh K.;Hashimoto, Takashi;Kanazawa, Kazuki
岩藻黄质是褐海藻中的一种主要类胡萝卜素，最近被我们证明可以抑制结肠癌细胞的增殖，并且这种作用与生长停滞有关。这些结果与之前对岩藻黄质的研究相结合，表明它可能有助于化学预防其他人类恶性肿瘤。本研究旨在利用人肝癌 HepG2 细胞系（HepG2）评估岩藻黄质抗肝癌的分子机制。 25 μM 的岩藻黄质降低了 HepG2 细胞的活力，同时诱导细胞周期停滞在 G(0)/G(1) 期。该浓度的岩藻黄质在治疗后抑制了视网膜母细胞瘤蛋白 (Rb) 在丝氨酸 780 (Ser780) 位置 18 It 的磷酸化。负责 Rb Ser780 位点磷酸化的细胞周期蛋白 D 和 cdk4 复合物的激酶活性在治疗后下调 18 It。蛋白质印迹分析显示，岩藻黄质处理抑制了细胞周期蛋白D型蛋白的表达。这种减少被蛋白酶体抑制剂 MG132 的同时治疗部分阻断，表明涉及蛋白酶体介导的降解。此外，RT-PCR 分析表明岩藻黄质似乎还抑制细胞周期蛋白 D mRNA。因此，蛋白质降解和转录抑制似乎都是岩藻黄质处理的 HepG2 细胞中细胞周期蛋白 D 水平受到抑制的原因，这可能与抗肿瘤活性有关。 (C) 2008 年由 Elsevier B.V. 出版
Fucoxanthin, a major carotenoid in brown sea algae, has recently been demonstrated by us to inhibit the proliferation of colon cancer cells, and this effect was associated with growth arrest. These results, taken together with previous studies with fucoxanthin, suggest that it may be useful in chemoprevention of other human malignancies. The present study was designed to evaluate the molecular mechanisms of fucoxanthin against hepatic cancer using the human hepatocarcinoma HepG2 cell line (HepG2). Fucoxanthin reduced the viability of HepG2 cells accompanied with the induction of cell cycle arrest during the G(0)/G(1) phase at 25 mu M. This concentration of fucoxanthin inhibited the phosphorylation of the retinoblastoma protein (Rb) at Serine 780 (Ser780) position 18 It after treatment. The kinase activity of cyclin D and cdk4 complex, responsible for the phosphorylation of Rb Ser780 site, was down-regulated 18 It after the treatment. Western blotting analysis revealed that the expression of cyclin D-type protein was suppressed by treatment of fucoxanthin. This reduction was partially blocked by concurrent treatment with the proteasome inhibitor MG132, indicating the involvement of the proteasome-mediated degradation. In addition, RT-PCR analysis revealed that fucoxanthin also appeared to repress cyclin D mRNA. Thus, both the protein degradation and transcriptional repression seem to be responsible for suppressed cyclin D level in fucoxanthin-treated HepG2 cells which may be related to the antitumorgenic activity. (C) 2008 Published by Elsevier B.V.