Brazilian marine sponge Polymastia janeirensis induces apoptotic cell death in human U138MG glioma cell line, but not in a normal cell culture.
Marine sponges have been prominently featured in the area of cancer research. Here, we examined the anti-proliferative effects of crude extracts (aqueous and organic) of the Brazilian marine sponge Polymastia janeirensis in the U138MG human glioma cell line. Moreover, we examined the effects of extracts on selective cytotoxicity in the glioma cells in comparison with a normal cell culture. Exposure of glioma cells to treatments (24 h) resulted in cell number decrease at all doses tested, with both aqueous and organic extracts (IC(50) <20 and <30 microg/ml, respectively). Parallel to this result, sponge extracts reduced glioma cell viability (IC(50) <15 microg/ml for both extracts). However, higher doses (50 and 100 microg/ml) induced a stronger cytotoxic effect when compared to the lower dose tested (10 microg/ml), inhibiting more than 80% of cellular growth and viability. Propidium iodide uptake and flow cytometry analysis further showed that sponge extracts caused necrosis in the glioma cell line at higher doses, while a high percentage of apoptotic glioma cells were observed at 10 microg/ml. Moreover, apoptosis was prevented by the pan-caspase inhibitor Z-VAD, suggesting that marine sponge extracts, at lower doses, induce caspase-dependent apoptosis in U138MG glioma cells. Surprisingly the extracts herein tested were more effective than temozolomide, a potent inductor of apoptosis used for the treatment of malignant gliomas. Furthermore, our results suggested a selectivity cytotoxic effect on glioma cell line in comparison with a normal cell culture, since the effect on viability found in glioma cells was not observed in astrocyte cultures with the lower dose (10 microg/ml). Thus, this marine sponge may be considered a good candidate for development of new cancer medicines with antitumor activity against gliomas.
da Frota
Mario Luiz Conte
ML
Centro de Estudos em Estresse Oxidativo (CEEO), ICBS, UFRGS, Porto Alegre, Brazil. mfrotajr@yahoo.com.br
Braganhol
Elizandra
E
Canedo
Andrés Delgado
AD
Klamt
Fabio
F
Apel
Miriam Anders
MA
Mothes
Beatriz
B
Lerner
Cléa
C
Battastini
Ana Maria Oliveira
AM
Henriques
Amélia Teresinha
AT
Moreira
José Cláudio Fonseca
JC
D000590:Amino Acid Chloromethyl Ketones / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects; D001938:Brazil; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000494:pharmacology*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D000077204:Temozolomide
D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D045424:Complex Mixtures; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D003606:Dacarbazine; D000077204:Temozolomide