Fucoxanthin enhances cisplatin-induced cytotoxicity via NFκB-mediated pathway and downregulates DNA repair gene expression in human hepatoma HepG2 cells.
Fucoxanthin enhances cisplatin-induced cytotoxicity via NFκB-mediated pathway and downregulates DNA repair gene expression in human hepatoma HepG2 cells.
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DOI：
10.3390/md11010050
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发表时间：
2013-01-08
期刊：
影响因子：
5.4
通讯作者：
Hu ML
中科院分区：
文献类型：
--
作者：
Liu CL;Lim YP;Hu ML
顺铂是一种含铂的抗癌药物，已被证明可以促进DNA修复和抑制细胞凋亡，从而导致耐药性。因此，抗癌药物与营养因素的结合是提高顺铂化疗疗效的潜在策略。在这项研究中，我们研究了裙带菜中发现的主要非维生素A原类胡萝卜素岩藻黄质与顺铂在人肝癌HepG2细胞中的联合抗增殖作用。我们发现，岩藻黄质(1-10μΜ)处理24 h后再用顺铂(10μΜ)处理24 h，与单独用顺铂处理相比，细胞增殖显著降低。从机制上讲，我们发现岩藻黄质减弱了顺铂诱导的NFκB的表达，并增强了NFκB调节的bax/bc l-2m RNA比率。顺铂通过磷酸化ERK、p38和PI3K/AKT通路诱导切除修复交叉互补1(ERCC1)和胸苷磷酸化酶(TP)的mRNA表达。而岩藻黄质可显著抑制顺铂诱导的ERCC1和TP基因的表达，从而提高顺铂的化疗疗效。这些结果表明，岩藻黄质和顺铂的联合治疗可能导致一种潜在的重要的针对人肝癌细胞的新治疗策略。
Cisplain, a platinum-containing anticancer drug, has been shown to enhance DNA repair and to inhibit cell apoptosis, leading to drug resistance. Thus, the combination of anticancer drugs with nutritional factors is a potential strategy for improving the efficacy of cisplatin chemotherapy. In this study, we investigated the anti-proliferative effects of a combination of fucoxanthin, the major non-provitamin A carotenoid found in Undaria Pinnatifida, and cisplatin in human hepatoma HepG2 cells. We found that fucoxanthin (1–10 μΜ) pretreatment for 24 h followed by cisplatin (10 μΜ) for 24 h significantly decreased cell proliferation, as compared with cisplatin treatment alone. Mechanistically, we showed that fucoxanthin attenuated cisplatin-induced NFκB expression and enhanced the NFκB-regulated Bax/Bcl-2 mRNA ratio. Cisplatin alone induced mRNA expression of excision repair cross complementation 1 (ERCC1) and thymidine phosphorylase (TP) through phosphorylation of ERK, p38 and PI3K/AKT pathways. However, fucoxanthin pretreatment significantly attenuated cisplatin-induced ERCC1 and TP mRNA expression, leading to improvement of chemotherapeutic efficacy of cisplatin. The results suggest that a combined treatment with fucoxanthin and cisplatin could lead to a potentially important new therapeutic strategy against human hepatoma cells.
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DOI：
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发表时间：
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影响因子：
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