title: Crocin Suppresses Constitutively Active STAT3 Through Induction of Protein Tyrosine Phosphatase SHP-1.
abstract: The aim of the present study is to investigate the effect of a natural compound crocin, one of the active components of saffron, on human multiple myeloma cells. Crocin effectively suppressed constitutive STAT3 activation, translocation of STAT3 to the nucleus, and its target gene expression. The suppression of STAT3 was mediated through the inhibition of activation of protein tyrosine kinases JAK1, JAK2, and c-Src. We found that crocin induced the expression of SHP-1, a tyrosine protein phosphatase, and pervanadate treatment reversed the crocin-induced downregulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Moreover, suppression of SHP-1 by its inhibitor overturned the effect of crocin on induction of SHP-1 and the inhibition of STAT3 activation. Finally, crocin downregulated the expression of STAT3-mediated gene products including anti-apoptotic (Bcl-2), pro-apoptotic (BAX), invasive (CXCR4), angiogenic (VEGF), and cell cycle regulator (cyclin D1), which are correlated with suppression of proliferation, the accumulation of cells in sub-G1 phase of cell cycle, and induction of apoptosis. Overall, our results suggested that crocin is a novel inhibitor of STAT3 activation pathway and thus may have potential in prevention and treatment of human multiple myeloma. J. Cell. Biochem. 118: 3290-3298, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Buyun
authors.initials: B
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Korea University, Sejong Campus 2511 Sejong-ro, Sejong City 339-770, Republic of Korea.
authors.forename: Ki Yong
authors.initials: KY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Byoungduck
authors.identifier: 0000-0002-3801-717X
authors.initials: B
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002338:Carotenoids / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D002338:Carotenoids; C029036:crocin; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: APOPTOSIS; CROCIN; SHP-1; STAT3