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Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma and implications in breast cancer.

ABSTRACT: Coffee contains several compounds that have the potential to influence breast cancer risk and survival. However, epidemiologic data on the relation between coffee compounds and breast cancer survival are sparse and inconsistent.We show that coffee component HHQ has significant apoptotic effect on MDA-MB-231 and MCF-7 cells in vitro, and that ROS generation, change in mitochondrial membrane permeability, upregulation of Bax and Caspase-8 as well as down regulation of PGK1 and PKM2 expression may be important apoptosis-inducing mechanisms. The results suggest that PPAR? ligands may serve as potential therapeutic agents for breast cancer therapy. HHQ was also validated as a ligand for PPAR? by docking procedure.This is the first report on the anti-breast cancer (in vitro) activity of HHQ.

SUBMITTER: Shashni B

PROVIDER: S-EPMC3852186 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma and implications in breast cancer.

Shashni Babita B Sharma Karun K Singh Rumani R Sakharkar Kishore R KR Dhillon Sarinder K SK Nagasaki Yukio Y Sakharkar Meena K MK

BMC genomics 20131016

<h4>Background</h4>Coffee contains several compounds that have the potential to influence breast cancer risk and survival. However, epidemiologic data on the relation between coffee compounds and breast cancer survival are sparse and inconsistent.<h4>Results</h4>We show that coffee component HHQ has significant apoptotic effect on MDA-MB-231 and MCF-7 cells in vitro, and that ROS generation, change in mitochondrial membrane permeability, upregulation of Bax and Caspase-8 as well as down regulati ...[more]

PMID: 24564733

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Project description:BackgroundPersistent fibroblast activation initiated by transforming growth factor β (TGF-β) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents a potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exerts potent fibrotic activity. The synthetic oleanane triterpenoid, 2-cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO), is a PPAR-γ agonist with potential effects on TGF-β signalling and dermal fibrosis.ObjectiveTo examine the modulation of fibrogenesis by CDDO in explanted fibroblasts, skin organ cultures and murine models of scleroderma.Material and methodsThe effects of CDDO on experimental fibrosis induced by bleomycin injection or by overexpression of constitutively active type I TGF-β receptor (TgfbR1ca) were evaluated. Modulation of fibrotic gene expression was examined in human skin organ cultures. To delineate the mechanisms underlying the antifibrotic effects of CDDO, explanted skin fibroblasts cultured in two-dimensional monolayers or in three-dimensional full-thickness human skin equivalents were studied.ResultsCDDO significantly ameliorated dermal fibrosis in two complementary mouse models of scleroderma, as well as in human skin organ cultures and in three-dimensional human skin equivalents. In two-dimensional monolayer cultures of explanted normal fibroblasts, CDDO abrogated fibrogenic responses induced by TGF-β. These CDDO effects occurred via disruption of Smad-dependent transcription and were associated with inhibition of Akt activation. In scleroderma fibroblasts, CDDO attenuated the elevated synthesis of collagen. Remarkably, the in vitro antifibrotic effects of CDDO were independent of PPAR-γ.ConclusionsThe PPAR-γ agonist triterpenoid CDDO attenuates fibrogenesis by antagonistically targeting canonical TGF-β/Smad and Akt signalling in a PPAR-γ-independent manner. These findings identify this synthetic triterpenoid as a potential new therapy for the control of fibrosis.

Dataset Information

Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma and implications in breast cancer.

Publications

Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma and implications in breast cancer.

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