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 α β for nonpeptide hormones. Interaction between hormones and integrin α β can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin α β . 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 β 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. .

Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation

“…DHT actins via integrin αvβ3 (Figure 1), behaving as a trophic agent for certain types of breast cancer cells [8]. Remarkably, the mechanisms involved in DHT-induced proliferative action differ between ER-α-negative and ER-α-positive cells in vitro.…”

“…To stimulate proliferation of breast cancer cells [7] Integrin αvβ3 NA [8] DHT Androgen Receptor (AR) To form ligand-AR complex and controlling gene expression To stimulate proliferation of prostate cancer cells. [9] Estrogen Receptor-α (ER-α) To stimulate proliferation of ER-positive breast cancer cells [7] Integrin αvβ3…”

Herbal Medicines Attenuate PD-L1 Expression to Induce Anti-Proliferation in Obesity-Related Cancers

“…This antioxidant stilbene has been shown to have anti-inflammatory effects [45]. Thus it has been discovered to have cardiovascular protective effects [46], anti-cancer proliferative effects [47,48], and anti-diabetic effects [49]. Resveratrol can attenuate the expression of pro-inflammatory genes [50].…”

“…Resveratrol can also induce anti-proliferation in various cancer cells [33,34,47] and inhibit cancer growth in vivo [53]. Resveratrol activates ERK1/2 via binding to the receptor on αvβ3 integrin.…”

“…Thyroid hormones and steroid hormones induce ERK1/2 activation via the cell surface integrin, αvβ3, and specific steroid hormone receptors [33,35,37,47,68]. Thyroxine activates ERK1/2 to stimulate β-catenin-HMGA2-dependent proliferation [69].…”