title: Buthionine sulfoximine and 1,25-dihydroxyvitamin D induce apoptosis in breast cancer cells via induction of reactive oxygen species.
abstract: Calcitriol or 1,25(OH)(2)D(3) is a negative growth regulator of breast cancer cells. The aim of this study was to determine whether L-buthionine-S,R-sulfoximine, a glutathione-depleting drug, modifies the antiproliferative effects of 1,25(OH)(2)D(3) on MCF-7 cells. For comparison, we included studies in MCF-7 cells selected for vitamin D resistance and in human mammary epithelial cells transformed with SV40 and ras. Our data indicate that L-buthionine-S,R-sulfoximine enhances the growth inhibition of 1,25(OH)(2)D(3) in all transformed breast cell lines. This effect is mediated by ROS leading to apoptosis. In conclusion, BSO alters redox state and sensitizes breast cancer cells to 1,25(OH)(2)D(3)-mediated apoptosis.
authors.affiliation: Laboratorio Dr. Fernando Cañas, Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba , Argentina.
authors.forename: Luciana P
authors.initials: LP
authors.lastname: Bohl
authors.forename: Ana C
authors.initials: AC
authors.lastname: Liaudat
authors.forename: Gabriela
authors.initials: G
authors.lastname: Picotto
authors.forename: Ana M
authors.initials: AM
authors.lastname: Marchionatti
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Narvaez
authors.forename: Joellen
authors.initials: J
authors.lastname: Welsh
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Rodriguez
authors.forename: Nori G
authors.initials: NG
authors.lastname: Tolosa de Talamoni
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014807:Vitamin D; D019328:Buthionine Sulfoximine; C097949:1,25-dihydroxyvitamin D; D020169:Caspases