Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells. Issue 5 (May 2018)

• Record Type: Journal Article
• Authors: Chin, Yu-Tang; Wei, Po-Li; Ho, Yih; Nana, André Wendindondé; Changou, Chun A; Chen, Yi-Ru; Yang, Yu-Chen SH; Hsieh, Meng-Ti; Hercbergs, Aleck; Davis, Paul J; Shih, Ya-Jung; Lin, Hung-Yun
• Is Part Of: Endocrine-related cancer. Volume 25:Issue 5(2018)
• Page Start: 533
• Page End: 545
• Publication Date: 2018-05
• Subjects: l-thyroxine -- resveratrol -- PD-L1 -- COX-2 -- ovarian cancer; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-17-0376
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : Thyroid hormone, l -thyroxine (T4 ), has been shown to promote ovarian cancer cell proliferation via a receptor on plasma membrane integrin αvβ3 and to induce the activation of ERK1/2 and expression of programmed death-ligand 1 (PD-L1) in cancer cells. In contrast, resveratrol binds to integrin αvβ3 at a discrete site and induces p53-dependent antiproliferation in malignant neoplastic cells. The mechanism of resveratrol action requires nuclear accumulation of inducible cyclooxygenase (COX)-2 and its complexation with phosphorylated ERK1/2. In this study, we examined the mechanism by which T4 impairs resveratrol-induced antiproliferation in human ovarian cancer cells and found that T4 inhibited resveratrol-induced nuclear accumulation of COX-2. Furthermore, T4 increased expression and cytoplasmic accumulation of PD-L1, which in turn acted to retain inducible COX-2 in the cytoplasm. Knockdown of PD-L1 by small hairpin RNA (shRNA) relieved the inhibitory effect of T4 on resveratrol-induced nuclear accumulation of COX-2- and COX-2/p53-dependent gene expression. Thus, T4 inhibits COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with PD-L1 in the cytoplasm. These findings provide new insights into the antagonizing effect of T4 on resveratrol's anticancer properties.