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.

Original languageEnglish
Pages (from-to)415-427
Number of pages13
JournalAmerican Journal of Chinese Medicine
Volume40
Issue number2
DOIs
Publication statusPublished - 2012

Fingerprint

Vascular Endothelial Growth Factor A
Interleukin-6
Small Interfering RNA
wogonin
Pathologic Neovascularization
Janus Kinases
Transducers
Endothelial Cells
Neoplasms
Proteins

Keywords

  • Angiogenesis
  • IL-6
  • JAK1/STAT3
  • VEGF
  • Wogonin

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Functional role of wogonin in anti-angiogenesis. / Lin, Chiu Mei; Chen, Yen Hsu; Ong, Jiann Ruey; Ma, Hon Ping; Shyu, Kou-Gi; Bai, Kuan Jen.

In: American Journal of Chinese Medicine, Vol. 40, No. 2, 2012, p. 415-427.

Research output: Contribution to journalArticle

Lin, Chiu Mei ; Chen, Yen Hsu ; Ong, Jiann Ruey ; Ma, Hon Ping ; Shyu, Kou-Gi ; Bai, Kuan Jen. / Functional role of wogonin in anti-angiogenesis. In: American Journal of Chinese Medicine. 2012 ; Vol. 40, No. 2. pp. 415-427.
@article{d26bfa20a80541ed91f9dc18eeea6b11,
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.",
keywords = "Angiogenesis, IL-6, JAK1/STAT3, VEGF, Wogonin",
author = "Lin, {Chiu Mei} and Chen, {Yen Hsu} and Ong, {Jiann Ruey} and Ma, {Hon Ping} and Kou-Gi Shyu and Bai, {Kuan Jen}",
year = "2012",
doi = "10.1142/S0192415X12500322",
language = "English",
volume = "40",
pages = "415--427",
journal = "American Journal of Chinese Medicine",
issn = "0192-415X",
publisher = "World Scientific Publishing Co. Pte Ltd",
number = "2",

}

TY - JOUR

T1 - Functional role of wogonin in anti-angiogenesis

AU - Lin, Chiu Mei

AU - Chen, Yen Hsu

AU - Ong, Jiann Ruey

AU - Ma, Hon Ping

AU - Shyu, Kou-Gi

AU - Bai, Kuan Jen

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - IL-6

KW - JAK1/STAT3

KW - VEGF

KW - Wogonin

UR - http://www.scopus.com/inward/record.url?scp=84863388470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863388470&partnerID=8YFLogxK

U2 - 10.1142/S0192415X12500322

DO - 10.1142/S0192415X12500322

M3 - Article

C2 - 22419433

AN - SCOPUS:84863388470

VL - 40

SP - 415

EP - 427

JO - American Journal of Chinese Medicine

JF - American Journal of Chinese Medicine

SN - 0192-415X

IS - 2

ER -