Mechanisms of action of nonpeptide hormones on resveratrol-induced antiproliferation of cancer cells

Hung Yun Lin, Meng Ti Hsieh, Guei Yun Cheng, Hsuan Yu Lai, Yu Tang Chin, Ya Jung Shih, André Wendindondé Nana, Shin Ying Lin, Yu Chen S.H. Yang, Heng Yuan Tang, I. Jen Chiang, Kuan Wang

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)


Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin αvβ3 for nonpeptide hormones. Interaction between hormones and integrin αvβ3 can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin αvβ3. Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin αvβ3 blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalAnnals of the New York Academy of Sciences
Issue number1
Publication statusPublished - 2017


  • Apoptosis
  • ERK1/2 phosphorylation
  • Nuclear COX-2 accumulation
  • Resveratrol
  • Steroid hormones

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • History and Philosophy of Science


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