@article{ada751751de74c459028560edf35d00b,
title = "Mechanisms of action of nonpeptide hormones on resveratrol-induced antiproliferation of cancer cells",
abstract = "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.",
keywords = "Apoptosis, ERK1/2 phosphorylation, Nuclear COX-2 accumulation, Resveratrol, Steroid hormones",
author = "Lin, {Hung Yun} and Hsieh, {Meng Ti} and Cheng, {Guei Yun} and Lai, {Hsuan Yu} and Chin, {Yu Tang} and Shih, {Ya Jung} and Nana, {Andr{\'e} Wendindond{\'e}} and Lin, {Shin Ying} and Yang, {Yu Chen S.H.} and Tang, {Heng Yuan} and Chiang, {I. Jen} and Kuan Wang",
note = "Funding Information: We dedicate this manuscript in memory of Mr. Ying-Chieh Lin for his endless support of our research. The authors also appreciate the excellent administrative work of Miss Ya-Jung Shih and Ms. Cindy Lee, who made it possible for Resveratrol2016 to be held at TMU, Taipei, Taiwan. Appreciation is sent to Miss Guei-Yun Cheng for her artistic work on the figure. Work from our laboratory described in this review article was supported in part by an endowment established by M. Frank and Margaret Domiter Rudy, a grant from the Ministry of Education (TMU Top University Fund), and grants from the Ministry of Science and Technology, Taiwan (MOST104-2314-B-038, -046, -MY3; MOST105-2320-B-038-006). Funding Information: 1PhD program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. 2Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. 3Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan. 4Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan. 5Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York. 6School of Health Care Administration. 7Graduate Institute of Nanomedicine and Medical Engineering, Taipei Medical University, Taipei, Taiwan Address for correspondence: Hung-Yun Lin, PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan. linhy@tmu.edu.tw Publisher Copyright: {\textcopyright} 2017 New York Academy of Sciences.",
year = "2017",
doi = "10.1111/nyas.13423",
language = "English",
volume = "1403",
pages = "92--100",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Blackwell Publishing Ltd",
number = "1",
}