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Title: Curcumin sensitizes lung adenocarcinoma cells to apoptosis via intracellular redox status mediated pathway
Authors: Kaushik, Gaurav
Kaushik, Toshi
Yadav, Subodh Kumar
Sharma, Sanjeev Kumar
Ranawat, Pavitra
Khanduja, Krishan Lal
Pathak, Chander Mohan
Keywords: A549 Cells;Adenocarcinoma;Apoptosis;Curcumin;MAPK signaling;Reactive oxygen species;Redox status
Issue Date: Dec-2012
Publisher: NISCAIR-CSIR, India
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 -glutamylcysteine synthetase (-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.
Page(s): 853-861
ISSN: 0975-1009 (Online); 0019-5189 (Print)
Appears in Collections:IJEB Vol.50(12) [December 2012]

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