title: Proteasomal Dysfunction Induced By Diclofenac Engenders Apoptosis Through Mitochondrial Pathway.
abstract: Diclofenac is the most commonly used phenylacetic acid derivative non-steroidal anti-inflammatory drug (NSAID) that demonstrates significant analgesic, antipyretic, and anti-inflammatory effects. Several epidemiological studies have demonstrated anti-proliferative activity of NSAIDs and examined their apoptotic induction effects in different cancer cell lines. However, the precise molecular mechanisms by which these pharmacological agents induce apoptosis and exert anti-carcinogenic properties are not well known. Here, we have observed that diclofenac treatment induces proteasome malfunction and promotes accumulation of different critical proteasome substrates, including few pro-apoptotic proteins in cells. Exposure of diclofenac consequently elevates aggregation of various ubiquitylated misfolded proteins. Finally, we have shown that diclofenac treatment promotes apoptosis in cells, which could be because of mitochondrial membrane depolarization and cytochrome c release into cytosol. This study suggests possible beneficial insights of NSAIDs-induced apoptosis that may improve our existing knowledge in anti-proliferative interspecific strategies development. J. Cell. Biochem. 118: 1014-1027, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
authors.forename: Ayeman
authors.initials: A
authors.lastname: Amanullah
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Upadhyay
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Chhangani
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
authors.forename: Vibhuti
authors.initials: V
authors.lastname: Joshi
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
authors.forename: Ribhav
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Department of Neuroscience and Pathobiology Research Institute of Environmental Medicine, Nagoya University Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, 342011, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Mishra
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004008:Diclofenac / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004008:Diclofenac; D046988:Proteasome Endopeptidase Complex
keywords: APOPTOSIS; CANCER; MITOCHONDRIA; NSAIDs; PROTEASOME