Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells

Yi Ru Chen; Yu Shen Chen; Yu Tang Chin; Zi Lin Li; Ya Jung Shih; Yu Chen S.H. Yang; Chun A. ChangOu; Po Yu Su; Shwu Huey Wang; Yun Hsuan Wu; Hsien Chung Chiu; Sheng Yang Lee; Leroy F. Liu; Jacqueline Whang-Peng; Hung Yun Lin; Shaker A. Mousa; Paul J. Davis; Kuan Wang

doi:10.1016/j.fct.2019.110693

Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells

Yi Ru Chen, Yu Shen Chen, Yu Tang Chin, Zi Lin Li, Ya Jung Shih, Yu Chen S.H. Yang, Chun A. ChangOu, Po Yu Su, Shwu Huey Wang, Yun Hsuan Wu, Hsien Chung Chiu, Sheng Yang Lee, Leroy F. Liu, Jacqueline Whang-Peng, Hung Yun Lin, Shaker A. Mousa, Paul J. Davis, Kuan Wang

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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.

Original language	English
Article number	110693
Journal	Food and Chemical Toxicology
Volume	132
DOIs	https://doi.org/10.1016/j.fct.2019.110693
Publication status	Published - Oct 2019

Keywords

Inflammation
L-thyroxine
Oral cancer
PD-L1
Resveratrol

ASJC Scopus subject areas

Food Science
Toxicology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.fct.2019.110693

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Chen, Y. R., Chen, Y. S., Chin, Y. T., Li, Z. L., Shih, Y. J., Yang, Y. C. S. H., ChangOu, C. A., Su, P. Y., Wang, S. H., Wu, Y. H., Chiu, H. C., Lee, S. Y., Liu, L. F., Whang-Peng, J., Lin, H. Y., Mousa, S. A., Davis, P. J., & Wang, K. (2019). Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells. Food and Chemical Toxicology, 132, Article 110693. https://doi.org/10.1016/j.fct.2019.110693

Chen, YR, Chen, YS, Chin, YT, Li, ZL, Shih, YJ, Yang, YCSH, ChangOu, CA, Su, PY, Wang, SH, Wu, YH, Chiu, HC, Lee, SY, Liu, LF, Whang-Peng, J , Lin, HY, Mousa, SA, Davis, PJ & Wang, K 2019, 'Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells', Food and Chemical Toxicology, vol. 132, 110693. https://doi.org/10.1016/j.fct.2019.110693

@article{0eb102d6eb314f36975da8abb5f1b378,

title = "Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells",

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.",

keywords = "Inflammation, L-thyroxine, Oral cancer, PD-L1, Resveratrol",

author = "Chen, {Yi Ru} and Chen, {Yu Shen} and Chin, {Yu Tang} and Li, {Zi Lin} and Shih, {Ya Jung} and Yang, {Yu Chen S.H.} and ChangOu, {Chun A.} and Su, {Po Yu} and Wang, {Shwu Huey} and Wu, {Yun Hsuan} and Chiu, {Hsien Chung} and Lee, {Sheng Yang} and Liu, {Leroy F.} and Jacqueline Whang-Peng and Lin, {Hung Yun} and Mousa, {Shaker A.} and Davis, {Paul J.} and Kuan Wang",

note = "Funding Information: This work was supported in part by an intra-institutional grant from E-Da Medical Center ( EDAHP108041 to Dr. Y.S. Chen), by a Research Award from the Dr. Ta-Cheng Tung Foundation, by the Chair Professor Research Fund to Dr. K. Wang, and to Dr. J. Whang-Peng, the “ TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, general grants from the Ministry of Science and Technology Taiwan ( MOST107-2314-B-038-017 to H.Y. Lin), and a gift from Dr. PJ Davis to Albany College of Pharmacy and Health Sciences. The authors would like to extend their most sincere appreciation to Miss Zi-Lin and Miss ABu for their prodigious contribution to this work. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = oct,

doi = "10.1016/j.fct.2019.110693",

language = "English",

volume = "132",

journal = "Food and Chemical Toxicology",

issn = "0278-6915",

publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells

AU - Chen, Yi Ru

AU - Chen, Yu Shen

AU - Chin, Yu Tang

AU - Li, Zi Lin

AU - Shih, Ya Jung

AU - Yang, Yu Chen S.H.

AU - ChangOu, Chun A.

AU - Su, Po Yu

AU - Wang, Shwu Huey

AU - Wu, Yun Hsuan

AU - Chiu, Hsien Chung

AU - Lee, Sheng Yang

AU - Liu, Leroy F.

AU - Whang-Peng, Jacqueline

AU - Lin, Hung Yun

AU - Mousa, Shaker A.

AU - Davis, Paul J.

AU - Wang, Kuan

N1 - Funding Information: This work was supported in part by an intra-institutional grant from E-Da Medical Center ( EDAHP108041 to Dr. Y.S. Chen), by a Research Award from the Dr. Ta-Cheng Tung Foundation, by the Chair Professor Research Fund to Dr. K. Wang, and to Dr. J. Whang-Peng, the “ TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, general grants from the Ministry of Science and Technology Taiwan ( MOST107-2314-B-038-017 to H.Y. Lin), and a gift from Dr. PJ Davis to Albany College of Pharmacy and Health Sciences. The authors would like to extend their most sincere appreciation to Miss Zi-Lin and Miss ABu for their prodigious contribution to this work. Publisher Copyright: © 2019

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - Inflammation

KW - L-thyroxine

KW - Oral cancer

KW - PD-L1

KW - Resveratrol

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UR - http://www.scopus.com/inward/citedby.url?scp=85069653678&partnerID=8YFLogxK

U2 - 10.1016/j.fct.2019.110693

DO - 10.1016/j.fct.2019.110693

M3 - Article

C2 - 31336132

AN - SCOPUS:85069653678

SN - 0278-6915

VL - 132

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

M1 - 110693

ER -

Thyroid hormone-induced expression of inflammatory cytokines interfere with resveratrol-induced anti-proliferation of oral cancer cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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