title: Ibuprofen Induces Mitochondrial-Mediated Apoptosis Through Proteasomal Dysfunction.
abstract: In routine course of life, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed antipyretic, analgesic, and anti-inflammatory drugs. It is a well-proposed notion that treatment of NSAIDs may induce anti-proliferative effects in numerous cancer cells. Ibuprofen from isobutylphenylpropanoic acid is NSAID and used to relieve fever, pain, and inflammation. It is also used for juvenile idiopathic arthritis, rheumatoid arthritis, patent ductus arteriosus, and for pericarditis. Despite few emerging studies have expanded the fundamental concept that the treatment of NSAIDs influences apoptosis in cancer cells, however the NSAID-mediated precise mechanisms that determine apoptosis induction without producing adverse consequences in variety of cancer cells are largely unknown. In our present study, we have observed that ibuprofen reduces proteasome activity, enhances the aggregation of ubiquitylated abnormal proteins, and also elevates the accumulation of crucial proteasome substrates. Ibuprofen treatment causes mitochondrial abnormalities and releases cytochrome c into cytosol. Perhaps, the more detailed study is needed in the future to elucidate the molecular mechanisms of NSAIDs that can induce apoptosis without adverse effects and produce effective anti-tumor effects and consequently help in neurodegeneration and ageing.
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India, 342011.
authors.forename: Arun
authors.initials: A
authors.lastname: Upadhyay
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India, 342011.
authors.forename: Ayeman
authors.initials: A
authors.lastname: Amanullah
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India, 342011.
authors.forename: Deepak
authors.initials: D
authors.lastname: Chhangani
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India, 342011.
authors.forename: Vibhuti
authors.initials: V
authors.lastname: Joshi
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India, 342011.
authors.forename: Ribhav
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India, 342011. amit@iitj.ac.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Mishra
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019556:COS Cells; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D053144:Cell Nucleus Shape / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D002479:Inclusion Bodies / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D066329:Protein Aggregates / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D013379:Substrate Specificity / Q000187:drug effects; D013997:Time Factors; D057149:Ubiquitinated Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D066329:Protein Aggregates; D057149:Ubiquitinated Proteins; D000072000:NF-KappaB Inhibitor alpha; D045304:Cytochromes c; D046988:Proteasome Endopeptidase Complex; D007052:Ibuprofen
keywords: Ageing; Apoptosis; Ibuprofen; Mitochondrial dysfunction; NSAIDs; Neurodegeneration; Proteasome