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.