Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China.
Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China.
Biochem Biophys Res Commun. 2014 May 23;448(1):15-21. doi: 10.1016/j.bbrc.2014.04.024. Epub 2014 Apr 13.
Here we studied the role of mitochondrial permeability transition pore (mPTP) opening in curcumin's cytotoxicity in melanoma cells. In cultured WM-115 melanoma cells, curcumin induced mitochondrial membrane potential (MPP) decrease, cyclophilin-D (CyPD)-adenine nucleotide translocator 1 (ANT-1) (two mPTP components) mitochondrial association and cytochrome C release, indicating mPTP opening. The mPTP blocker sanglifehrin A (SfA) and ANT-1 siRNA-depletion dramatically inhibited curcumin-induced cytochrome C release and WM-115 cell death. CyPD is required for curcumin-induced melanoma cell death. The CyPD inhibitor cyclosporin A (CsA) or CyPD siRNA-depletion inhibited curcumin-induced WM-115 cell death and apoptosis, while WM-115 cells with CyPD over-expression were hyper-sensitive to curcumin. Finally, we found that C6 ceramide enhanced curcumin-induced cytotoxicity probably through facilitating mPTP opening, while CsA and SfA as well as CyPD and ANT-1 siRNAs alleviated C6 ceramide's effect on curcumin in WM-115 cells. Together, these results suggest that curcumin-induced melanoma cell death is associated with mPTP opening.
在这里，我们研究了线粒体通透性转换孔（mPTP）开放在姜黄素对黑素瘤细胞毒性中的作用。在培养的 WM-115 黑素瘤细胞中，姜黄素诱导线粒体膜电位（MPP）下降、亲环素 D（CyPD）-腺嘌呤核苷酸转运蛋白 1（ANT-1）（两个 mPTP 组成部分）线粒体结合和细胞色素 C 释放，表明 mPTP 开放。mPTP 阻断剂桑弗林 A（SfA）和 ANT-1 siRNA 耗竭显著抑制姜黄素诱导的细胞色素 C 释放和 WM-115 细胞死亡。CyPD 是姜黄素诱导黑素瘤细胞死亡所必需的。CyPD 抑制剂环孢菌素 A（CsA）或 CyPD siRNA 耗竭抑制姜黄素诱导的 WM-115 细胞死亡和凋亡，而 CyPD 过表达的 WM-115 细胞对姜黄素高度敏感。最后，我们发现 C6 神经酰胺增强了姜黄素的细胞毒性，可能是通过促进 mPTP 开放，而 CsA、SfA 以及 CyPD 和 ANT-1 siRNA 减轻了 C6 神经酰胺对 WM-115 细胞中姜黄素的作用。总之，这些结果表明姜黄素诱导的黑素瘤细胞死亡与 mPTP 开放有关。
