Brazilian marine sponge Polymastia janeirensis induces apoptotic cell death in human U138MG glioma cell line, but not in a normal cell culture

• Published in: Investigational new drugs Vol. 27; no. 1; pp. 13 - 20
• Main Authors: da Frota, Mario Luiz Conte, Braganhol, Elizandra, Canedo, Andrés Delgado, Klamt, Fabio, Apel, Miriam Anders, Mothes, Beatriz, Lerner, Cléa, Battastini, Ana Maria Oliveira, Henriques, Amélia Teresinha, Moreira, José Cláudio Fonseca
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2009; Springer Nature B.V
• Subjects: Amino Acid Chloromethyl Ketones - antagonists & inhibitors; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Aquatic life; Astrocytes - drug effects; Brain cancer; Brazil; Cancer therapies; Cell culture; Cell death; Cell Line, Transformed; Cell Line, Tumor; Complex Mixtures - pharmacology; Cytotoxicity; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Drug dosages; Glioma - drug therapy; Humans; Medical prognosis; Medicine; Medicine & Public Health; Oncology; Pharmaceutical sciences; Pharmacology/Toxicology; Polymastia janeirensis; Porifera - chemistry; Preclinical Studies; Tumors; Marine sponges; New drugs; Glioma cells; Cancer; Apoptosis
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-008-9134-3

Summary 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 μg/ml, respectively). Parallel to this result, sponge extracts reduced glioma cell viability (IC 50 <15 μg/ml for both extracts). However, higher doses (50 and 100 μg/ml) induced a stronger cytotoxic effect when compared to the lower dose tested (10 μg/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 μg/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 μg/ml). Thus, this marine sponge may be considered a good candidate for development of new cancer medicines with antitumor activity against gliomas.