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Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells.
- Source :
-
Endocrine-related cancer [Endocr Relat Cancer] 2018 May; Vol. 25 (5), pp. 533-545. Date of Electronic Publication: 2018 Mar 19. - Publication Year :
- 2018
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Abstract
- Thyroid hormone, l-thyroxine (T <subscript>4</subscript> ), 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 T <subscript>4</subscript> impairs resveratrol-induced antiproliferation in human ovarian cancer cells and found that T <subscript>4</subscript> inhibited resveratrol-induced nuclear accumulation of COX-2. Furthermore, T <subscript>4</subscript> 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 T <subscript>4</subscript> on resveratrol-induced nuclear accumulation of COX-2- and COX-2/p53-dependent gene expression. Thus, T <subscript>4</subscript> 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 T <subscript>4</subscript> on resveratrol's anticancer properties.<br /> (© 2018 Society for Endocrinology.)
Details
- Language :
- English
- ISSN :
- 1479-6821
- Volume :
- 25
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Endocrine-related cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29555649
- Full Text :
- https://doi.org/10.1530/ERC-17-0376