Curcumin analogue GO-Y030 inhibits STAT3 activity and cell growth in breast and pancreatic carcinomas.
Curcumin has numerous anti-carcinogenic properties, but low bioavailability prevents its use in chemotherapeutic applications. One strategy for circumventing this problem has been the creation of synthetic analogues. We tested the efficacy of an analogue known as GO-Y030 in human breast and pancreatic cancer cells. We compared the impact of curcumin and GO-Y030 on the breast cancer cell line MDA-MB-231 and pancreatic cancer cell lines, PANC-1, HPAC and BXPC-3. Both compounds reduced cell viability and induced apoptosis, but GO-Y030 was substantially more potent. We also demonstrated that GO-Y030 was capable of interfering with STAT3, a persistently activated transcription factor in many cancer types. GO-Y030 inhibited STAT3 phosphorylation and transcriptional activity whereas comparable dosages of curcumin had little or no effect. These results indicate that GO-Y030 is a potent inhibitor of cell viability and STAT3 activation, and may thus have potential as a therapeutic agent for cancers expressing high levels of activated STAT3.
Hutzen
Brian
B
Department of Pediatrics, Tohoku University, Sendai, Japan.
Friedman
Lauren
L
Sobo
Matthew
M
Lin
Li
L
Cen
Ling
L
De Angelis
Stephanie
S
Yamakoshi
Hiroyuki
H
Shibata
Hiroyuki
H
Iwabuchi
Yoshiharu
Y
Lin
Jiayuh
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; C541486:GO-Y030 compound; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D003474:Curcumin