title: Curcumin sensitizes lung adenocarcinoma cells to apoptosis via intracellular redox status mediated pathway.
abstract: The present study demonstrates that curcumin acts as pro-oxidant and sensitizes human lung adenocarcinoma epithelial cells (A549) to apoptosis via intracellular redox status mediated pathway. Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. These events seem to be mediated through generation of reactive oxygen species (ROS) and superoxide radicals (SOR) and enhanced levels of lipid peroxidation. These changes were accompanied by increase in oxidized glutathione (GSSG), reduced glutathione (GSH) and gamma-glutamylcysteine synthetase (gamma-GCS) activity, but decrease in GSH/GSSG ratio. The induction of apoptosis and decrease in GSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. However, L-buthionine sulfoximine (BSO), a GSH synthesis blocking agent, further enhanced curcumin-induced ROS production and apoptosis in A549 cells. Decreased GSH/GSSG ratio seems to be a crucial factor for the activation of MAPK signaling cascade by curcumin. The study therefore, provides an insight into the molecular mechanism involved in sensitization of lung adenocarcinoma cells to apoptosis by curcumin.
authors.affiliation: Department of Biophysics, Post Graduate Institute of Medical Education and Research, Chandigarh 160 012, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaushik
authors.forename: Toshi
authors.initials: T
authors.lastname: Kaushik
authors.forename: Subodh Kumar
authors.initials: SK
authors.lastname: Yadav
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Pavitra
authors.initials: P
authors.lastname: Ranawat
authors.forename: Krishan Lal
authors.initials: KL
authors.lastname: Khanduja
authors.forename: Chander Mohan
authors.initials: CM
authors.lastname: Pathak
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000230:Adenocarcinoma / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis / Q000235:genetics; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008175:Lung Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D016877:Oxidants; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017382:Reactive Oxygen Species; D013481:Superoxides; D019328:Buthionine Sulfoximine; C505407:CASP3 protein, human; D053148:Caspase 3; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003474:Curcumin; D000111:Acetylcysteine