Cancer Lett. 2012 Jan 20. [Epub ahead of print]
Targeting heat shock factor 1 with a triazole nucleoside analog to elicit potent anticancer activity on drug-resistant pancreatic cancer.
Aix-Marseille Université, Centre Interdisciplinaire de Nanoscience de Marseille, CNRS UMR 7325, 163 avenue de Luminy, 13288 Marseille, France.
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.
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