Resveratrol inhibits human leiomyoma cell proliferation via crosstalk between integrin αvβ3 and IGF-1R

Yih Ho, Yu Chen SH Yang, Yu Tang Chin, Szu Yi Chou, Yi Ru Chen, Ya Jung Shih, Jacqueline Whang-Peng, Chun A. Changou, Hsuan Liang Liu, Shwu Jiuan Lin, Heng Yuan Tang, Hung Yun Lin, Paul J. Davis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Leiomyomas (myomas) are the most common benign smooth muscle cell tumor of the myometrium. Resveratrol, a stilbene, has been used as an anti-inflammatory and antitumor agent. In the current study, we investigated the inhibitory effect of resveratrol on the proliferation of primary human myoma cell cultures. Resveratrol arrested cell proliferation via integrin αvβ3. It also inhibited integrin αvβ3 expression and protein accumulation. Concurrently, constitutive AKT phosphorylation in myoma cells was inhibited by resveratrol. Expressions of proapoptotic genes, such as cyclooxygenase (COX)-2, p21 and CDKN2, were induced by resveratrol in myoma cells. On the other hand, expressions of proliferative (anti-apoptotic) genes were either inhibited, as in BCL2, or unchanged, as in cyclin D1 and proliferating cell nuclear antigen (PCNA). The accumulation of insulin-like growth factor (IGF)-1 receptor (IGF-1R) was inhibited by resveratrol in primary myoma cells. IGF-1-induced cell proliferation was inhibited by co-incubation with resveratrol. Therefore, growth modulation of myoma cells occurs via mechanisms dependent on cross-talk between integrin αvβ3 and IGF-1R. Our findings suggest that resveratrol can be considered an alternative therapeutic agent for myomas.

Original languageEnglish
Pages (from-to)346-355
Number of pages10
JournalFood and Chemical Toxicology
Volume120
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

resveratrol
integrins
Myoma
Cell proliferation
somatomedins
Leiomyoma
Somatomedins
Crosstalk
Integrins
cell proliferation
Cell Proliferation
Genes
cells
Smooth Muscle Tumor
Somatomedin Receptors
myometrium
anti-inflammatory agents
Stilbenes
proliferating cell nuclear antigen
Phosphorylation

Keywords

  • Anti-Proliferation
  • Integrin αvβ3
  • Leiomyoma
  • Stilbenes

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Resveratrol inhibits human leiomyoma cell proliferation via crosstalk between integrin αvβ3 and IGF-1R. / Ho, Yih; SH Yang, Yu Chen; Chin, Yu Tang; Chou, Szu Yi; Chen, Yi Ru; Shih, Ya Jung; Whang-Peng, Jacqueline; Changou, Chun A.; Liu, Hsuan Liang; Lin, Shwu Jiuan; Tang, Heng Yuan; Lin, Hung Yun; Davis, Paul J.

In: Food and Chemical Toxicology, Vol. 120, 01.10.2018, p. 346-355.

Research output: Contribution to journalArticle

Ho, Yih ; SH Yang, Yu Chen ; Chin, Yu Tang ; Chou, Szu Yi ; Chen, Yi Ru ; Shih, Ya Jung ; Whang-Peng, Jacqueline ; Changou, Chun A. ; Liu, Hsuan Liang ; Lin, Shwu Jiuan ; Tang, Heng Yuan ; Lin, Hung Yun ; Davis, Paul J. / Resveratrol inhibits human leiomyoma cell proliferation via crosstalk between integrin αvβ3 and IGF-1R. In: Food and Chemical Toxicology. 2018 ; Vol. 120. pp. 346-355.
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AU - SH Yang, Yu Chen

AU - Chin, Yu Tang

AU - Chou, Szu Yi

AU - Chen, Yi Ru

AU - Shih, Ya Jung

AU - Whang-Peng, Jacqueline

AU - Changou, Chun A.

AU - Liu, Hsuan Liang

AU - Lin, Shwu Jiuan

AU - Tang, Heng Yuan

AU - Lin, Hung Yun

AU - Davis, Paul J.

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AB - Leiomyomas (myomas) are the most common benign smooth muscle cell tumor of the myometrium. Resveratrol, a stilbene, has been used as an anti-inflammatory and antitumor agent. In the current study, we investigated the inhibitory effect of resveratrol on the proliferation of primary human myoma cell cultures. Resveratrol arrested cell proliferation via integrin αvβ3. It also inhibited integrin αvβ3 expression and protein accumulation. Concurrently, constitutive AKT phosphorylation in myoma cells was inhibited by resveratrol. Expressions of proapoptotic genes, such as cyclooxygenase (COX)-2, p21 and CDKN2, were induced by resveratrol in myoma cells. On the other hand, expressions of proliferative (anti-apoptotic) genes were either inhibited, as in BCL2, or unchanged, as in cyclin D1 and proliferating cell nuclear antigen (PCNA). The accumulation of insulin-like growth factor (IGF)-1 receptor (IGF-1R) was inhibited by resveratrol in primary myoma cells. IGF-1-induced cell proliferation was inhibited by co-incubation with resveratrol. Therefore, growth modulation of myoma cells occurs via mechanisms dependent on cross-talk between integrin αvβ3 and IGF-1R. Our findings suggest that resveratrol can be considered an alternative therapeutic agent for myomas.

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