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Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells
Author(s) -
Lin HungYun,
Hsieh MengTi,
Cheng GueiYun,
Lai HsuanYu,
Chin YuTang,
Shih YaJung,
Nana André Wendindondé,
Lin ShinYing,
Yang YuChen S.H.,
Tang HengYuan,
Chiang IJen,
Wang Kuan
Publication year - 2017
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13423
Subject(s) - resveratrol , chemistry , hormone , receptor , microbiology and biotechnology , signal transduction , cancer cell , pharmacology , biology , biochemistry , medicine , cancer
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 α v β 3 for nonpeptide hormones. Interaction between hormones and integrin α v β 3 can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX‐2–dependent antiproliferation via integrin α v β 3 . 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 α v β 3 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.