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新型姜黄素类似物 EF24 对人卵巢癌细胞的多种抗癌活性。

Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.

机构信息

Department of Vascular Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Reprod Sci. 2010 Oct;17(10):931-40. doi: 10.1177/1933719110374239. Epub 2010 Aug 6.

Abstract

Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.

摘要

姜黄素是姜黄的一种成分,据报道具有潜在的抗肿瘤活性。本研究评估了一种新型合成姜黄素类似物 EF24 对铂敏感(IGROV1)和铂耐药(SK-OV-3)人卵巢癌细胞增殖、凋亡和血管内皮生长因子(VEGF)调节的影响。EF24 呈时间和剂量依赖性抑制两种细胞系的生长,并与顺铂协同诱导凋亡。尽管 EF24 处理对 VEGF 信使 RNA(mRNA)表达没有显著影响,但 EF24 可剂量依赖性地下调 VEGF 蛋白向条件培养基中的分泌,其效力比姜黄素高约 8 倍(P <.05)。EF24 可显著抑制过氧化氢(H 2 O 2 )诱导的 VEGF 表达,酚类抗氧化剂叔丁基对苯二酚(t-BHQ)也是如此。EF24 通过抑制活性氧(ROS)的产生和激活抗氧化反应元件(ARE)依赖性基因转录来上调细胞抗氧化反应。鉴于其高效力,EF24 是作为卵巢癌临床前模型中辅助治疗剂进一步开发的极佳先导候选物。

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