Novel triazole ribonucleoside down-regulates heat shock protein 27 and induces potent anticancer activity on drug-resistant pancreatic cancer.
A series of novel 3-arylethynyltriazolyl ribonucleosides were synthesized and assessed for their anticancer activity on the drug-resistant pancreatic cancer cell line MiaPaCa-2. Among them, one compound exhibited potent apoptosis-inducing properties and anticancer activity against the pancreatic cancer model MiaPaCa-2 both in vitro and in vivo with no adverse effects. This compound did not inhibit DNA synthesis and therefore does not resemble the clinical drug gemcitabine. It did, however, significantly down-regulate the expression of heat shock protein 27 (Hsp27), a small molecular chaperone playing an important role in drug resistance and highly expressed in drug-resistant cancer forms, and thus represents the first small molecular anticancer lead with such a mode of action.
Xia
Yi
Y
State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, PR China.
Liu
Yang
Y
Wan
Jinqiao
J
Wang
Menghua
M
Rocchi
Palma
P
Qu
Fanqi
F
Iovanna
Juan L
JL
Peng
Ling
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D055551:HSP27 Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012263:Ribonucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D055551:HSP27 Heat-Shock Proteins; D012263:Ribonucleosides; D014230:Triazoles