title: Caffeine augments Alprazolam induced cytotoxicity in human cell lines.
abstract: Combined effects of alprazolam (Alp), a member of benzodiazepine group of drugs and caffeine on human cell lines, HeLa and THP1 were investigated in this study. Alp mediated cytotoxicity was enhanced while caffeine was present. The cell death was confirmed by observing morphological changes, LDH assay and membrane anisotropic study. Also such combined effects induced elevated level of ROS and depletion of GSH. The mechanism of cell death induced by simultaneous treatment of Alp and caffeine was associated with the calcium-mediated activation of mu-calpain, release of lysosomal protease cathepsin B, activation of PARP and cleavage of caspase 3. Our results indicate that, Alp alone induces apoptosis in human cells but in the presence of caffeine it augments necrosis in a well-regulated pathway. Thus our observations strongly suggest that, alprazolam and caffeine together produce severe cytotoxicity in human cell lines.
authors.affiliation: Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700 032, West Bengal, India.
authors.forename: Biswarup
authors.initials: B
authors.lastname: Saha
authors.forename: Ananda
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Saheli
authors.initials: S
authors.lastname: Samanta
authors.forename: Piyali
authors.initials: P
authors.lastname: Saha
authors.forename: Anup Kumar
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Chitta Ranjan
authors.initials: CR
authors.lastname: Santra
authors.forename: Parimal
authors.initials: P
authors.lastname: Karmakar
mesh_terms: D000525:Alprazolam / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D000697:Central Nervous System Stimulants; D017382:Reactive Oxygen Species; D002110:Caffeine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D000525:Alprazolam