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Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells
- Source :
- Food and Chemical Toxicology. 132:110693
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Thyroid hormone, L-thyroxine (T4), induces inflammatory genes expressions and promotes cancer growth. It also induces expression of the checkpoint programmed death-ligand 1 (PD-L1), which plays a vital role in cancer progression. On the other hand, resveratrol inhibits inflammatory genes expressions. Moreover, resveratrol increases nuclear inducible cyclooxygenase (COX)-2 accumulation, complexes with p53, and induces p53-dependent anti-proliferation. In this study, we investigated the effect of T4 on resveratrol-induced anti-proliferation in oral cancer. T4 increased the expression and cytoplasmic accumulation of PD-L1. Increased expressions of pro-inflammatory genes, interleukin (IL)-1β and transforming growth factor (TGF)-β1, were shown to stimulate PD-L1 expression. T4 stimulated pro-inflammatory and proliferative genes expressions, and oral cancer cells proliferation. In contrast, resveratrol inhibited those genes and activated anti-proliferative genes. T4 retained resveratrol-induced COX-2 in cytoplasm and prevented COX-2 nuclear accumulation when resveratrol treated cancer cells. A specific signal transducer and activator of transcription 3 (STAT3) inhibitor, S31-201, blocked T4-induced inhibition and restored resveratrol-induced nuclear COX-2 accumulation. By inhibiting the T4-activated STAT3 signal transduction axis with S31-201, resveratrol was able to sequentially reestablish COX-2/p53-dependent gene expressions and anti-proliferation. These findings provide a novel understanding of the inhibitory effects of T4 on resveratrol-induced anticancer properties via the sequential expression of PD-L1 and inflammatory genes.
- Subjects :
- STAT3 Transcription Factor
Gene Expression
Resveratrol
Toxicology
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
0404 agricultural biotechnology
Cell Line, Tumor
Gene expression
medicine
Humans
STAT3
Cell Proliferation
030304 developmental biology
Cell Nucleus
0303 health sciences
biology
Cancer
04 agricultural and veterinary sciences
General Medicine
medicine.disease
040401 food science
Thyroxine
chemistry
Cyclooxygenase 2
Cancer cell
biology.protein
STAT protein
Cancer research
Cytokines
Mouth Neoplasms
Inflammation Mediators
Signal transduction
Food Science
Subjects
Details
- ISSN :
- 02786915
- Volume :
- 132
- Database :
- OpenAIRE
- Journal :
- Food and Chemical Toxicology
- Accession number :
- edsair.doi.dedup.....dbf750aac5be9382f0b2a28ba07ed88b