title: Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy.
abstract: Resveratrol has been shown to exhibit its anti-cancer effect through a variety of mechanisms. Here, TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) was identified as an important target of resveratrol for exhibiting ROS-dependent-consequences on apoptosis and autophagy. Resveratrol treatment decreased TIGAR protein irrespective of cell line used. Down-regulated TIGAR protein triggered a drop in reduced-glutathione levels which resulted in sustained ROS, responsible for apoptosis and autophagy. Over-expression and silencing experiments demonstrated the importance of TIGAR in affecting the ROS-dependent anti-cancer effects of resveratrol. Resveratrol treated cells exhibited autophagy to escape apoptosis, however, chloroquine treatment along with resveratrol, blocked protective autophagy and facilitated apoptosis. Collectively, results unravel the effects of resveratrol on TIGAR in mediating its ROS dependent influence and suggest a better combination therapy of resveratrol and chloroquine for probable cancer treatment.
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Bhupender
authors.initials: B
authors.lastname: Kumar
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Mohammad Askandar
authors.initials: MA
authors.lastname: Iqbal
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Rajnish Kumar
authors.initials: RK
authors.lastname: Singh
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: bamezai@hotmail.com.
authors.forename: Rameshwar N K
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004357:Drug Synergism; D005455:Fluorescent Antibody Technique; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D018613:Microscopy, Confocal; D010744:Phosphoric Monoester Hydrolases; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002738:Chloroquine; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human; D000077185:Resveratrol
keywords: Apoptosis; Autophagy; Resveratrol; TIGAR