Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.

Trans-3,5-dimethoxy-4'-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear recep...

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Autores principales:	Kumar Nikhil, Shruti Sharan, Abhimanyu K Singh, Ajanta Chakraborty, Partha Roy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c0b65f71ac544d788a595b831c9bfe3
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spelling	oai:doaj.org-article:2c0b65f71ac544d788a595b831c9bfe32021-11-25T06:04:54ZAnticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.1932-620310.1371/journal.pone.0104592https://doaj.org/article/2c0b65f71ac544d788a595b831c9bfe32014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119466/?tool=EBIhttps://doaj.org/toc/1932-6203Trans-3,5-dimethoxy-4'-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway.Kumar NikhilShruti SharanAbhimanyu K SinghAjanta ChakrabortyPartha RoyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104592 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kumar Nikhil Shruti Sharan Abhimanyu K Singh Ajanta Chakraborty Partha Roy Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.
description	Trans-3,5-dimethoxy-4'-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway.
format	article
author	Kumar Nikhil Shruti Sharan Abhimanyu K Singh Ajanta Chakraborty Partha Roy
author_facet	Kumar Nikhil Shruti Sharan Abhimanyu K Singh Ajanta Chakraborty Partha Roy
author_sort	Kumar Nikhil
title	Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.
title_short	Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.
title_full	Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.
title_fullStr	Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.
title_full_unstemmed	Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.
title_sort	anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of pparγ.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2c0b65f71ac544d788a595b831c9bfe3
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Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARγ.

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