title: Bromelain-induced apoptosis in GI-101A breast cancer cells.
abstract: Bromelain is a proteolytic enzyme extracted from the stems and the immature fruits of pineapple that was found to be antitumorigenic in different in vitro models. Bromelain has been reported to promote apoptosis, particularly in breast cancer cells, with the up-regulation of c-Jun N-terminal kinase and p38 kinase. Our study was designed to determine if bromelain could induce apoptosis in GI-101A breast cancer cells. GI-101A cells were treated with increasing concentrations of bromelain for 24 hours. The effect of bromelain for inducing cell death via activation of the apoptosis mechanism in GI-101A cells was further determined by using caspase-9 and caspase-3 assays along with the M30-Apoptosense assay to measure cytokeratin 18 (CK18) levels in the cytoplasm of the cultured cancer cells. A dose-dependent increase in the activities of caspase-9 and caspase-3 coinciding with elevation of CK18 levels was found in bromelain-treated cells compared with control cells. Furthermore, the apoptosis induction by bromelain was confirmed by DNA fragmentation analysis and 4,6'-diamino-2-phenylindole dihydrochloride fluorescence staining of the nucleus. Our results indicate an increase in apoptosis-related cell death in breast cancer cells with increasing concentrations of bromelain.
authors.affiliation: Rumbaugh Goodwin Institute for Cancer Research, Health Professions Division, Nova Southeastern University, Fort Lauderdale, Florida 33313, USA.
authors.forename: Sivanesan
authors.initials: S
authors.lastname: Dhandayuthapani
authors.forename: Honey Diaz
authors.initials: HD
authors.lastname: Perez
authors.forename: Alexandra
authors.initials: A
authors.lastname: Paroulek
authors.forename: Panneerselvam
authors.initials: P
authors.lastname: Chinnakkannu
authors.forename: Umadevi
authors.initials: U
authors.lastname: Kandalam
authors.forename: Mark
authors.initials: M
authors.lastname: Jaffe
authors.forename: Appu
authors.initials: A
authors.lastname: Rathinavelu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D001963:Bromelains / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: C488421:KRT18 protein, human; D053538:Keratin-18; D001963:Bromelains; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9