Sánchez Ana María, Martínez-Botas Javier, Malagarie-Cazenave Sophie, Olea Nuria, Vara Diana, Lasunción Miguel Angel, Díaz-Laviada Inés
Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, 28871 Alcala de Henares, Madrid, Spain.
Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91. doi: 10.1016/j.bbrc.2008.05.138. Epub 2008 Jun 3.
The effect of capsaicin, main pungent ingredient of hot chilli peppers, in the gene expression profile of human prostate PC-3 cancer cells has been analyzed using a microarray approach. We identified 10 genes that were down-regulated and five genes that were induced upon capsaicin treatment. The data obtained from microarray analysis were then validated using quantitative real-time PCR assays and Western blot analysis. The most remarkable change was the up-regulation of GADD153/CHOP, an endoplasmic reticulum stress-regulated gene. Activation of GADD153/CHOP protein was corroborated by immunofluorescence and Western blot. We then tested the contribution of GADD153/CHOP to protection against capsaicin-induced cell death using RNA interference. Blockage of GADD153/CHOP expression by small interfering RNA, significantly reduced capsaicin-induced cell death in PC-3 cells. Taken together, these results suggested that capsaicin induces the antiproliferative effect through a mechanism facilitated by ER stress in prostate PC-3 cells.
采用微阵列方法分析了辣椒中主要辛辣成分辣椒素对人前列腺PC-3癌细胞基因表达谱的影响。我们鉴定出10个下调基因和5个经辣椒素处理后被诱导的基因。然后使用定量实时PCR分析和蛋白质印迹分析对从微阵列分析中获得的数据进行验证。最显著的变化是内质网应激调节基因GADD153/CHOP的上调。免疫荧光和蛋白质印迹证实了GADD153/CHOP蛋白的激活。然后我们使用RNA干扰测试了GADD153/CHOP对抵御辣椒素诱导的细胞死亡的作用。小干扰RNA阻断GADD153/CHOP表达可显著降低辣椒素诱导的PC-3细胞死亡。综上所述,这些结果表明辣椒素通过内质网应激促进的机制诱导前列腺PC-3细胞产生抗增殖作用。