Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line

• Published in: Investigational new drugs Vol. 27; no. 5; pp. 440 - 446
• Main Authors: Conte da Frota, Mario Luiz, Braganhol, Elizandra, Delgado Canedo, Andrés, Klamt, Fabio, Apel, Miriam Anders, Mothes, Beatriz, Lerner, Cléa, Oliveira Battastini, Ana Maria, Henriques, Amélia Teresinha, Fonseca Moreira, José Cláudio
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2009; Springer Nature B.V
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Aquatic life; Biological products; Brain; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Caspase 9 - metabolism; Cell culture; Cell death; Cytotoxicity; Drug dosages; Experiments; Flow Cytometry; Glioma - drug therapy; Glioma - pathology; Humans; Medicine; Medicine & Public Health; Metabolites; Oncology; Pharmacology; Pharmacology/Toxicology; Polymastia janeirensis; Porifera - chemistry; Preclinical Studies; Reactive Oxygen Species - metabolism; Tissue Extracts - pharmacology; Tumor Cells, Cultured; Tumors; Marine sponges; Reactive oxygen species; Cancer; Apoptosis
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-008-9198-0

Summary 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 μg/mL has decreased glioma cell viability, with an IC 50 <15 μg/mL for both aqueous and organic extracts. However, extracts at higher doses (50 and 100 μg/mL) have stronger cytotoxic effects, decreasing more than 90% of glioma cell viability. The antioxidant Trolox® (100 μM) reversed the cell death percentage induced by extracts at 10 and 25 μg/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 μg/mL. Moreover, inhibition of caspase-8 with Z-IETD (a caspase-8 inhibitor) had no effect on the amount of apoptosis induced by 10 μg/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 μg/mL. This is a first report demonstrating that marine sponge extracts of P. janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway.