MARINE ASCIDIAN DIDEMNUM SP. COMPOUNDS CITOTOXICITY FOR HUMAN GLIOBLASTOMA CELLS

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  • Presentation type: DR - Doctoral Student
  • Track: Drugs and/or Natural Products Therapy
  • Keywords: Ascidian; Glioblastoma; Didemnum sp; anti-tumor; marine natural compounds;
  • 1 Programa Associado de Pós-Graduação em Biotecnologia Marinha (PPGBM) - Instituto de Estudos do Mar Almirante Paulo Moreira (IEAPM) - Universidade Federal Fluminense (UFF)
  • 2 Departamento de Biotecnologia Marinha (IEAPM)
  • 3 (PPGBM (IEAPM/UFF); Instituto de Biodiversidade e Sustentabilidade - Universidade Federal do Rio de Janeiro (UFRJ)
  • 4 Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA)
  • 5 PPGBM (IEAPM/UFF); Departamento de Biotecnologia Marinha (IEAPM)
  • 6 Instituto de Estudos do Mar Almirante Paulo Moreira (IEAPM) e Instituto Nacional de Câncer (INCA)

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Abstract

INTRODUCTION AND OBJECTIVES: Glioblastoma (GBM) is the most invasive malignant tumors in the Central Nervous System. Marine bioprospecting is a relevant anti-tumoral strategy in natural products field. Ascidian compounds have already found applications in cancer treatment, neurodegenerative and other diseases. The aim of this study is to evaluate cytotoxic and cytostatic effect of the ascidian Didemnum sp. extract and isolated/combined compounds in glioblastoma cells.

MATERIAL AND METHODS: We used the dynamic maceration process with 1:5 proportion methanol as solvent. After filtration, the solvent was evaporated at 50oC in a water bath, obtaining Didemnum sp. pull extract sample. Cytosolic acid phosphatase activity was used for cell viability assay by spectrophotometry and cell cycle was observed by flow cytometry. GBM cell lines T98G and U251, and a healthy cell line of human fibroblast BJ-5ta (IHF) were tested in a monolayer model, using increasing concentrations of the Didemnum sp. extract for 72h. Cell morphology was observed by contrast phase and DAPI staining.

RESULTS AND CONCLUSION: Didemnum sp. crude extract demonstrated significant anti-tumoral activity for T98G and U251 monolayers, with IC50 of 120.6 µg/mL and 63.32 µg/mL, respectively. Also, there was a relevant reduction of total DAPI+ cells percentual in both cell lines, and no cytotoxicity in IHF cells. However, no alteration in cell cycle phases was demonstrated. Such effectiveness demonstrates the anti-tumor potential of the Didemnum sp. extract. We expect to isolate the alkaloids and fatty acid identified by LC/MS/MS chromatography to test compound association strategies comparing to the crude extract in healthy and tumoral cells of the CNS in vitro, by spheroid model, and in vivo, by orthotopic model in C57BL6 mice. We suggest marine bioproducts candidates for GBM treatment as new and selective strategies in the future.

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