Targeting heat shock factor 1 with a triazole nucleoside analog to elicit potent anticancer activity on drug-resistant pancreatic cancer

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• 作者：Yi Xia^a ; Yang Liu^b ; Palma Rocchi^c ; Menghua Wang^a ; ^b ; Yuting Fan^b ; Fanqi Qu^b ; Juan L. Iovanna^c ; Ling Peng^a ; ^{ling.peng@univmed.fr}
• 关键词：Heat shock factor 1 ; Heat shock proteins ; Heat shock response pathway ; Triazole nucleoside ; Pancreatic cancer
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 May, 2012
• 卷：318
• 期：2
• 页码：145-153
• 文件大小：867 K

摘要

Issued from a lead optimization process, we have identified a novel triazole nucleoside analog which elicits potent anticancer activity on drug-resistant pancreatic cancer. Most importantly, this compound targets heat shock response pathways by down-regulation of heat shock transcription factor 1 and consequential down-regulation of multiple heat shock proteins HSP27, HSP70 and HSP90. Down-regulation of these proteins caused the shut-down of several oncogenic pathways and caspase-dependent apoptosis resulting in a potent anticancer effect in vitro and in vivo. These results demonstrate the potential rewards gained in searching for anticancer candidates with multimodal actions on heat shock response pathways via HSF1 down-regulation.