Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress.
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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DOI：
10.1038/srep10420
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发表时间：
2015-05-27
影响因子：
4.6
通讯作者：
Lee LM
中科院分区：
文献类型：
--
作者：
Lee WJ;Chien MH;Chow JM;Chang JL;Wen YC;Lin YW;Cheng CW;Lai GM;Hsiao M;Lee LM
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对癌症的治疗效果。据报道，姜黄素具有癌症化学预防特性。在此，我们报告姜黄素诱导LNCaP，DU 145和PC-3细胞的凋亡，但在PC-3 M细胞中引发广泛的细胞质空泡化。电镜观察表明，空泡缺乏胞内细胞器，来源于内质网（ER）。此外，姜黄素诱导的空泡化不能被细胞凋亡或自噬相关抑制剂逆转，这表明空泡介导的细胞死亡与经典的细胞凋亡和自噬细胞死亡不同。机制研究表明，姜黄素治疗上调ER应激标志物CHOP和Bip/GRP 78和自噬标志物LC 3-II。此外，姜黄素通过触发ROS产生诱导ER应激，这得到了用抗氧化剂NAC处理细胞减轻姜黄素介导的ER应激和空泡介导的死亡的发现的支持。体内PC-3 M原位前列腺癌模型显示，姜黄素通过诱导ROS产生，随后是空泡介导的细胞死亡来减少肿瘤生长。总的来说，我们的研究结果表明，姜黄素作为一种诱导剂的活性氧产生，这导致非凋亡和非自噬细胞死亡，通过增加内质网应激。
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.
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影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Chang PC;Wang TY;Chang YT;Chu CY;Lee CL;Hsu HW;Zhou TA;Wu Z;Kim RH;Desai SJ;Liu S;Kung HJ
通讯作者：
Kung HJ
影响因子：
8
作者：
Kar, R.;Singha, P. K.;Venkatachalam, M. A.;Saikumar, P.
通讯作者：
Saikumar, P.
影响因子：
4.5
作者：
McKnight NC;Zhong Y;Wold MS;Gong S;Phillips GR;Dou Z;Zhao Y;Heintz N;Zong WX;Yue Z
通讯作者：
Yue Z