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姜黄素诱导的人膀胱癌细胞有丝分裂纺锤体缺陷和细胞周期阻滞部分是通过抑制极光激酶 A 实现的。

Curcumin-induced mitotic spindle defect and cell cycle arrest in human bladder cancer cells occurs partly through inhibition of aurora A.

机构信息

Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Mol Pharmacol. 2011 Oct;80(4):638-46. doi: 10.1124/mol.111.072512. Epub 2011 Jul 14.

Abstract

Curcumin, an active compound in turmeric and curry, has been proven to induce tumor apoptosis and inhibit tumor proliferation, invasion, angiogenesis, and metastasis via modulating numerous targets in various types of cancer cells. Aurora A is a mitosis-related serine-threonine kinase and plays important roles in diverse human cancers. However, the effect of curcumin on Aurora A has not been reported. In this study, Aurora A promoter activity and mRNA expression were inhibited in curcumin-treated human bladder cancer T24 cells, suggesting that Aurora A is regulated at the transcription level. We also found that curcumin preferentially inhibited the growth of T24 cells, which show a higher proliferation rate, invasion activity, and expression level of Aurora A compared with that of human immortalized uroepithelial E7cells. Furthermore, inhibition of phosphorylation of Aurora A and its downstream target histone H3 accompanied by the formation of monopolar spindle, induction of G(2)/M phase arrest, and reduction in cell division in response to curcumin were detected in T24 cells. These curcumin-induced phenomena were similar to those using Aurora A small interfering RNA and were attenuated by ectopic expression of Aurora A. Therefore, the antitumor mechanism of curcumin is Aurora A-related, which further supports the application of curcumin in treatments of human cancers.

摘要

姜黄素是姜黄和咖喱中的一种活性化合物,已被证明通过调节各种类型癌细胞中的众多靶点来诱导肿瘤细胞凋亡并抑制肿瘤增殖、侵袭、血管生成和转移。Aurora A 是一种有丝分裂相关的丝氨酸-苏氨酸激酶,在多种人类癌症中发挥重要作用。然而,姜黄素对 Aurora A 的影响尚未报道。在这项研究中,姜黄素处理的人膀胱癌 T24 细胞中 Aurora A 启动子活性和 mRNA 表达受到抑制,表明 Aurora A 在转录水平受到调节。我们还发现姜黄素优先抑制 T24 细胞的生长,与永生化人尿路上皮 E7 细胞相比,T24 细胞具有更高的增殖率、侵袭活性和 Aurora A 的表达水平。此外,在 T24 细胞中检测到 Aurora A 及其下游靶标组蛋白 H3 的磷酸化抑制伴随着单极纺锤体的形成、G2/M 期阻滞的诱导和细胞分裂的减少。这些姜黄素诱导的现象类似于使用 Aurora A 小干扰 RNA 的现象,并且通过 Aurora A 的异位表达而减弱。因此,姜黄素的抗肿瘤机制与 Aurora A 相关,这进一步支持了姜黄素在人类癌症治疗中的应用。

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