title: Functional role of wogonin in anti-angiogenesis.
abstract: Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs commonly in cancer cells and endothelial cells, and contributes to angiogenesis. Wogonin is a compound with many biologically relevant properties. We previously reported that wogonin blocked IL-6-induced angiogenesis through suppression of VEGF expression, an important regulator of angiogenesis. However, the pathway involved in the suppressive effect of wogonin on IL-6-induced VEGF has not been completely clarified. This study aimed to investigate the molecular mechanisms participating in the suppression of wogonin on IL-6-induced VEGF in vitro, focusing on IL-6R/JAK1/STAT3/VEGF pathway. Both STAT3 siRNA and wogonin treatment resulted in an abolition of the expression of VEGF. Moreover, our data revealed that wogonin treatment after STAT3 knock-down did not further suppress VEGF expression. The addition of IL-6R siRNA or wogonin resulted in a decrease in the expression level of the phosphorylated JAK1 protein. Furthermore, wogonin significantly decreased the amount of phosphorylated STAT3. Finally, by EMSA, wogonin suppressed IL-6-induced STAT3 binding activity in a concentration-dependent manner. Taken together, our results show that wogonin suppresses IL-6-induced VEGF by modulating the IL-6R/JAK1/STAT3 signaling pathway. Based on this study, we suggest that wogonin may provide a new potential therapeutic option for treatment of IL-6-related pathological angiogenesis.
authors.affiliation: Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95 Wen-Cheng Road, Shin Lin, Taipei, Taiwan.
authors.forename: Chiu-Mei
authors.initials: CM
authors.lastname: Lin
authors.forename: Yen-Hsu
authors.initials: YH
authors.lastname: Chen
authors.forename: Jiann-Ruey
authors.initials: JR
authors.lastname: Ong
authors.forename: Hon-Ping
authors.initials: HP
authors.lastname: Ma
authors.forename: Kou-Gi
authors.initials: KG
authors.lastname: Shyu
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Bai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000009:adverse effects / Q000378:metabolism; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D053613:Janus Kinase 1; C085514:wogonin