Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer

Abstract Ovarian cancer is a highly aggressive disease and novel treatments are required. Thyroid hormones binding to αvβ3 integrin produced growth-promoting activities in ovarian cancer and we hypothesized that natural thyroid hormone derivatives may antagonize these actions. The effect of three an...

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Autores principales:	Elena Shinderman-Maman, Keren Cohen, Dotan Moskovich, Aleck Hercbergs, Haim Werner, Paul J. Davis, Martin Ellis, Osnat Ashur-Fabian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0387e756b4e9437087dee0edd92fdf52
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spelling	oai:doaj.org-article:0387e756b4e9437087dee0edd92fdf522021-12-02T15:05:44ZThyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer10.1038/s41598-017-16593-x2045-2322https://doaj.org/article/0387e756b4e9437087dee0edd92fdf522017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16593-xhttps://doaj.org/toc/2045-2322Abstract Ovarian cancer is a highly aggressive disease and novel treatments are required. Thyroid hormones binding to αvβ3 integrin produced growth-promoting activities in ovarian cancer and we hypothesized that natural thyroid hormone derivatives may antagonize these actions. The effect of three antagonists, tetraiodoacetic acid (tetrac), triiodothyroacetic acid (triac) and 3-iodothyronamine (T1AM), on cell proliferation, cell death and DNA damage was studied in two ovarian cancer cell lines (OVCAR3 and A2780), normal hamster ovary control cells (CHOK1) and αvβ3-deficient or transfected HEK293 cells. A differential inhibition of cell proliferation was observed in ovarian cancer cells compared to CHOK1. In OVCAR3, an induction of cell cycle regulators was further shown. Apoptosis was confirmed (annexin-PI, SubG1/cell-cycle, apoptotic genes, caspase-3 and poly ADP ribose polymerase-1 (PARP-1) cleavage) and was reversed by a pan-caspase inhibitor. Induction in apoptosis inducing factor (AIF) was observed, suggesting a parallel caspase-independent mechanism. Integrin-involvement in triac/T1AM apoptotic action was shown in αvβ3-transfected HEK293 cells. Lastly, in ovarian cancer models, key proteins that coordinate recognition of DNA damage, ataxia-telangiectasia mutated (ATM) and PARP-1, were induced. To conclude, the cytotoxic potential of thyroid hormone derivatives, tetrac, triac and T1AM, in ovarian cancer may provide a much-needed novel therapeutic approach.Elena Shinderman-MamanKeren CohenDotan MoskovichAleck HercbergsHaim WernerPaul J. DavisMartin EllisOsnat Ashur-FabianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elena Shinderman-Maman Keren Cohen Dotan Moskovich Aleck Hercbergs Haim Werner Paul J. Davis Martin Ellis Osnat Ashur-Fabian Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer
description	Abstract Ovarian cancer is a highly aggressive disease and novel treatments are required. Thyroid hormones binding to αvβ3 integrin produced growth-promoting activities in ovarian cancer and we hypothesized that natural thyroid hormone derivatives may antagonize these actions. The effect of three antagonists, tetraiodoacetic acid (tetrac), triiodothyroacetic acid (triac) and 3-iodothyronamine (T1AM), on cell proliferation, cell death and DNA damage was studied in two ovarian cancer cell lines (OVCAR3 and A2780), normal hamster ovary control cells (CHOK1) and αvβ3-deficient or transfected HEK293 cells. A differential inhibition of cell proliferation was observed in ovarian cancer cells compared to CHOK1. In OVCAR3, an induction of cell cycle regulators was further shown. Apoptosis was confirmed (annexin-PI, SubG1/cell-cycle, apoptotic genes, caspase-3 and poly ADP ribose polymerase-1 (PARP-1) cleavage) and was reversed by a pan-caspase inhibitor. Induction in apoptosis inducing factor (AIF) was observed, suggesting a parallel caspase-independent mechanism. Integrin-involvement in triac/T1AM apoptotic action was shown in αvβ3-transfected HEK293 cells. Lastly, in ovarian cancer models, key proteins that coordinate recognition of DNA damage, ataxia-telangiectasia mutated (ATM) and PARP-1, were induced. To conclude, the cytotoxic potential of thyroid hormone derivatives, tetrac, triac and T1AM, in ovarian cancer may provide a much-needed novel therapeutic approach.
format	article
author	Elena Shinderman-Maman Keren Cohen Dotan Moskovich Aleck Hercbergs Haim Werner Paul J. Davis Martin Ellis Osnat Ashur-Fabian
author_facet	Elena Shinderman-Maman Keren Cohen Dotan Moskovich Aleck Hercbergs Haim Werner Paul J. Davis Martin Ellis Osnat Ashur-Fabian
author_sort	Elena Shinderman-Maman
title	Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer
title_short	Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer
title_full	Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer
title_fullStr	Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer
title_full_unstemmed	Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer
title_sort	thyroid hormones derivatives reduce proliferation and induce cell death and dna damage in ovarian cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0387e756b4e9437087dee0edd92fdf52
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Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer

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