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首页> 外文期刊>Scientific reports. >Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress
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Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress

机译：姜黄素通过活性氧介导的内质网应激诱导人PC-3M前列腺癌非自噬性细胞质空泡死亡

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The antiapoptotic and antiautophagic abilities of cancer cells constitute a major challenge for anticancer drug treatment. Strategies for triggering nonapoptotic or nonautophagic cell death may improve therapeutic efficacy against cancer. Curcumin has been reported to exhibit cancer chemopreventive properties. Herein, we report that curcumin induced apoptosis in LNCaP, DU145, and PC-3 cells but triggered extensive cytoplasmic vacuolation in PC-3M cells. Electron microscopic images showed that the vacuoles lacked intracellular organelles and were derived from the endoplasmic reticulum (ER). Moreover, curcumin-induced vacuolation was not reversed by an apoptosis- or autophagy-related inhibitor, suggesting that vacuolation-mediated cell death differs from classical apoptotic and autophagic cell death. Mechanistic investigations revealed that curcumin treatment upregulated the ER stress markers CHOP and Bip/GRP78 and the autophagic marker LC3-II. In addition, curcumin induced ER stress by triggering ROS generation, which was supported by the finding that treating cells with the antioxidant NAC alleviated curcumin-mediated ER stress and vacuolation-mediated death. An in vivo PC-3M orthotopic prostate cancer model revealed that curcumin reduced tumor growth by inducing ROS production followed by vacuolation-mediated cell death. Overall, our results indicated that curcumin acts as an inducer of ROS production, which leads to nonapoptotic and nonautophagic cell death via increased ER stress.
机译：癌细胞的抗凋亡和抗自噬能力构成了抗癌药物治疗的主要挑战。触发非凋亡或非自噬性细胞死亡的策略可能会提高针对癌症的治疗功效。据报道姜黄素具有癌症化学预防特性。在本文中，我们报道姜黄素诱导LNCaP，DU145和PC-3细胞凋亡，但在PC-3M细胞中引发广泛的细胞质空泡化。电子显微镜图像显示，液泡缺乏细胞内细胞器，并且源自内质网（ER）。此外，姜黄素诱导的空泡化没有被凋亡或自噬相关抑制剂逆转，这表明空泡化介导的细胞死亡不同于经典的凋亡和自噬细胞死亡。机理研究表明，姜黄素治疗上调了ER应激标志物CHOP和Bip / GRP78以及自噬标志物LC3-II。此外，姜黄素通过触发ROS生成来诱导内质网应激，这一发现得到了支持，即使用抗氧化剂NAC处理细胞可减轻姜黄素介导的内质网应激和空泡化介导的死亡。体内PC-3M原位前列腺癌模型显示姜黄素通过诱导ROS产生，随后空泡介导的细胞死亡来减少肿瘤的生长。总体而言，我们的结果表明姜黄素可作为ROS的诱导剂，通过增加ER压力导致非凋亡和非自噬细胞死亡。

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