title: Mitochondrial dysfunction contributes to the cytotoxicity of some 3,5-bis(benzylidene)-4-piperidone derivatives in colon HCT-116 cells.
abstract: The objectives of this study are to investigate the possible ways by which the curcumin analogs 2a and 2b exert their antiproliferative properties. The analogs 2a and 2b have submicromolar IC(50) values towards human HCT-116 colon cancer cells but are far less toxic to human non-malignant CRL-1790 colon cells. Both compounds affected a number of mitochondrial functions in HCT-116 cells namely increasing the intracellular concentrations of reactive oxygen species, inhibiting oxygen consumption and decreasing the mitochondrial membrane potential. These molecules also produced swelling of isolated rat liver mitochondria, supporting a mitochondrial mechanism of cytotoxicity. Both compounds reacted with glutathione in the presence of glutathione S-transferase π and hence they may be classified as thiol alkylators.
authors.affiliation: Drug Design and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5C9.
authors.forename: Muath
authors.initials: M
authors.lastname: Helal
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Brian
authors.initials: B
authors.lastname: Bandy
authors.forename: Azharul
authors.initials: A
authors.lastname: Islam
authors.forename: Adil J
authors.initials: AJ
authors.lastname: Nazarali
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010881:Piperidones / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C526290:3,5-bis(benzylidene)-4-piperidone; D010881:Piperidones; D017382:Reactive Oxygen Species; D005978:Glutathione