Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cells
Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cells
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DOI：
10.1016/j.canlet.2010.04.018
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发表时间：
2010-11-01
期刊：
影响因子：
9.7
通讯作者：
Hoskin, David W.
中科院分区：
文献类型：
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作者：
Watson, Jane L.;Hill, Richard;Hoskin, David W.
来自姜黄植物根茎的姜黄素具有化学预防活性并抑制肿瘤细胞的生长。由于 p53 被认为对姜黄素的抗癌活性很重要，因此我们研究了姜黄素在 p53(+/+) 和 p53(-/-) HCT-116 结肠癌细胞以及突变型 p53 HT-29 结肠癌细胞培养物中诱导的细胞毒性。姜黄素以剂量和时间依赖性方式杀死野生型 p53 HCT-116 细胞和突变型 p53 HT-29 细胞。此外，姜黄素处理的p53（+/+）HCT-116细胞和突变型p53 HT-29细胞显示总p53和活化p53的上调，以及p53调节的p21、PUMA（p53上调的细胞凋亡调节剂）和Bax表达的增加：然而，在p53（+/+）和p53（-/-）HCT-116中观察到姜黄素具有同等的细胞毒性作用细胞，证明姜黄素诱导的细胞毒性与 p53 状态无关。当 siRNA 介导的 p53 敲低后，在野生型 p53 HCT-116 细胞中评估姜黄素的细胞毒性作用时，得到了类似的结果。姜黄素处理的 p53(+/+) 和 p53(-/-) HCT-116 细胞中染色质缩合、聚 (ADP-核糖) 聚合酶-1 裂解和前 caspase-3 水平降低表明姜黄素引起细胞凋亡。此外，暴露于姜黄素会导致p53(+/+)和p53(-/-) HCI-116细胞中超氧阴离子的产生和氧化应激蛋白的磷酸化。总的来说，我们的结果表明，尽管 p53 上调和激活，姜黄素诱导的结肠癌细胞凋亡与 p53 状态无关，并且涉及氧化应激。因此，姜黄素可能在结肠癌的治疗中具有治疗潜力，特别是对于由于 p53 表达或功能缺陷而对常规化疗产生耐药性的肿瘤。 (C) 2010 Elsevier Ireland Ltd. 保留所有权利。
Curcumin from the rhizome of the Curcuma longa plant has chemopreventative activity and inhibits the growth of neoplastic cells. Since p53 has been suggested to be important for anticancer activity by curcumin, we investigated curcumin-induced cytotoxicity in cultures of p53(+/+) and p53(-/-) HCT-116 colon cancer cells, as well as mutant p53 HT-29 colon cancer cells. Curcumin killed wild-type p53 HCT-116 cells and mutant p53 HT-29 cells in a dose- and time-dependent manner. In addition, curcumin-treated p53(+/+) HCT-116 cells and mutant p53 HT-29 cells showed upregulation of total and activated p53, as well as increased expression of p53-regulated p21, PUMA (p53 upregulated modulator of apoptosis), and Bax: however, an equivalent cytotoxic effect by curcumin was observed in p53(+/+) and p53(-/-) HCT-116 cells, demonstrating that curcumin-induced cytotoxicity was independent of p53 status. Similar results were obtained when the cytotoxic effect of curcumin was assessed in wild-type p53 HCT-116 cells after siRNA-mediated p53 knockdown. Chromatin condensation, poly (ADP-ribose) polymerase-1 cleavage and reduced pro-caspase-3 levels in curcumin-treated p53(+/+) and p53(-/-) HCT-116 cells suggested that curcumin caused apoptosis. In addition, exposure to curcumin resulted in superoxide anion production and phosphorylation of oxidative stress proteins in p53(+/+) and p53(-/-) HCI-116 cells. Collectively, our results indicate that, despite p53 upregulation and activation, curcumin-induced apoptosis in colon cancer cells was independent of p53 status and involved oxidative stress. Curcumin may therefore have therapeutic potential in the management of colon cancer, especially in tumors that are resistant to conventional chemotherapy due to defects in p53 expression or function. (C) 2010 Elsevier Ireland Ltd. All rights reserved.