Polyphenol tri-vanillic ester 13c inhibits P-JAK2V617F and Bcr-Abl oncokinase expression in correlation with STAT3/STAT5 inactivation and apoptosis induction in human leukemia cells
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- 作者：Anne Tr¨¦cul ; Franck Morceau ; Anthoula Gaigneaux ; Marion Orsini ; S¨¦bastien Chateauvieux ; Cindy Gr ; jenette ; Mario Dicato ; Marc Diederich
- 关键词：Kinase ; JAK2 ; Bcr&ndash ; Abl ; 13c ; Polyphenol ; STAT
- 刊名：Cancer Letters
- 出版年：2013
- 出版时间：28 October, 2013
- 年：2013
- 卷：340
- 期：1
- 页码：30-42
- 全文大小：2562 K
文摘
Constitutive activity of kinases has been reported in many types of cancers, so that inhibition of ¡°onco-kinases¡± became a validated anti-cancer strategy. We found that the polyphenol 13c, a tri-vanillate derivative, inhibited kinase phosphorylation in leukemia cells. P-JAK2, P-Src and P-PI3Kp85 inhibition occurred independently of phosphatase involvement in JAK2V617F expressing HEL cells while 13c inhibited Bcr-Abl expression without inhibition of phosphorylation in chronic myelogenous leukemia cell lines (K562, MEG-01). In correlation with kinase inhibition, 13c abolished constitutive P-STAT3/P-STAT5 expression, down-regulated Mcl-1 and c-Myc gene expression and induced apoptosis. Altogether, polyphenol 13c displays potential antitumor activities by affecting onco-kinases and STAT activities.