title: Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line.
abstract: We have studied the apoptotic pathway activated in response to marine sponge extracts of Polymastia janeirensis. The effect on intracellular ROS production was also examined. Exposure of U138MG glioma cell line to doses higher than 5 microg/mL has decreased glioma cell viability, with an IC(50) <15 microg/mL for both aqueous and organic extracts. However, extracts at higher doses (50 and 100 microg/mL) have stronger cytotoxic effects, decreasing more than 90% of glioma cell viability. The antioxidant Trolox (100 microM) reversed the cell death percentage induced by extracts at 10 and 25 microg/mL. The type of cell death induced by such high doses was predominantly necrosis, while a high percentage of apoptotic glioma cells was found at 10 microg/mL. Moreover, inhibition of caspase-8 with Z-IETD (a caspase-8 inhibitor) had no effect on the amount of apoptosis induced by 10 microg/mL, but inhibition of caspase-9 with Z-LEHD (a caspase-9 inhibitor) decreased apoptosis. We also observed a dose-dependent increase in ROS production, and similarly to effects observed on viability of glioma cells, and on cell death, higher doses also had more severe effects. Co-treatment with Trolox significantly reduced ROS production by extracts at doses lower than 50 microg/mL. This is a first report demonstrating that marine sponge extracts of P. janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway.
authors.affiliation: Centro de Estudos em Estresse Oxidativo (CEEO), ICBS-UFRGS, Porto Alegre, Brazil. mfrotajr@yahoo.com.br
authors.forename: Mario Luiz Conte
authors.initials: ML
authors.lastname: da Frota
authors.forename: Elizandra
authors.initials: E
authors.lastname: Braganhol
authors.forename: Andrés Delgado
authors.initials: AD
authors.lastname: Canedo
authors.forename: Fabio
authors.initials: F
authors.lastname: Klamt
authors.forename: Miriam Anders
authors.initials: MA
authors.lastname: Apel
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothes
authors.forename: Cléa
authors.initials: C
authors.lastname: Lerner
authors.forename: Ana Maria Oliveira
authors.initials: AM
authors.lastname: Battastini
authors.forename: Amélia Teresinha
authors.initials: AT
authors.lastname: Henriques
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053453:Caspase 9 / Q000378:metabolism*; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D017382:Reactive Oxygen Species; D014020:Tissue Extracts; D053453:Caspase 9