title: Targeting heat shock factor 1 with a triazole nucleoside analog to elicit potent anticancer activity on drug-resistant pancreatic cancer.
abstract: 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.
authors.affiliation: Aix-Marseille Université, Centre Interdisciplinaire de Nanoscience de Marseille, Marseille, France.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Palma
authors.initials: P
authors.lastname: Rocchi
authors.forename: Menghua
authors.initials: M
authors.lastname: Wang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Fan
authors.forename: Fanqi
authors.initials: F
authors.lastname: Qu
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D006360:Heat-Shock Proteins; D014230:Triazoles