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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/1104
Title: Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: Involvement of PPAR?
Authors: Nikhil K.
Sharan S.
Singh A.K.
Chakraborty A.
Roy P.
Published in: PLoS ONE
Abstract: 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 ? (PPAR?), 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 PPAR? involvement in PTER-ITC action. Our results showed that when pre-treated with PPAR? antagonists or PPAR? 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 PPAR? mRNA and protein levels in a dose-dependent manner and modulated expression of PPAR?-related genes in both breast cancer cell lines. This increase in PPAR? activity was prevented by a PPAR?-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPAR? activator. PTER-ITC-mediated upregulation of PPAR? was counteracted by coincubation 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 PPAR? ligandbinding 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 PPAR? activation pathway. © 2014 Nikhil et al.
Citation: PLoS ONE (2014), 9(8): -
URI: https://doi.org/10.1371/journal.pone.0104592
http://repository.iitr.ac.in/handle/123456789/1104
Issue Date: 2014
Publisher: Public Library of Science
ISSN: 19326203
Author Scopus IDs: 57192281884
55661549600
57209902397
8507454000
35509207200
Author Affiliations: Nikhil, K., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
Sharan, S., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
Singh, A.K., Department of Macromolecular Structures, Centro Nacional de Biotecnologia (CNB-CSIC), Campus de Cantoblanco, Madrid, Spain
Chakraborty, A., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
Roy, P., Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
Appears in Collections:Journal Publications [BT]

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