4-Nerolidylcatechol induces autophagy in human glioblastoma cells

Autor(es)

Renato Ramos Massaro ^[1] ; Carla Abdo Brohem ^[1] ; Rebeca Leite de Almeida ^[1] ; Diogo Pineda Rivelli ^[1] ; Juliano Andreoli Miyake ^[2] ; Alison Colquhoun ^[2] ; Silvia Berlanga de Moraes Barros ^[1] ; Silvya Stuchi Maria-Engler ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cell Biol & Dev, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Pharmaceutical Sciences; v. 53, n. 3 2018-02-01.

Resumo

ABSTRACT Gliomas account for the majority of primary malignant brain tumors and present invasive behavior into adjacent healthy tissue. While 4-NC had previously shown to induce apoptotic cell death in a melanoma model, for the glioma model described in this paper 4-NC is cytotoxic for the cells with the induction of the autophagic pathway. Trypan blue exclusion assay showed that 4-NC was cytotoxic in a dose-dependent manner for A172 and T98G cell lines. IC10 and IC50 values were at 32 µM and 41 µM for A172 and T98G respectively. Inhibition of cell proliferation was observed by total cell counts and by cell cycle analysis by flow cytometry, with cell cycle arrest of A172 and T98G cell lines respectively in the G1/G0 and S phases of the cell cycle. 4-NC induced up-regulation of autophagic pathways, as shown by immunoblotting for LC3-I/II, Real-Time PCR for ATG-7 and Beclin-1 genes, and by fluorescence microscopy observation of autophagic vacuoles in cells transfected with GFP-LC3 and electron microscopy. Glioma cells concomitantly treated with 4-NC and 3-MA, an inhibitor of the autophagic process, are more sensible to cell death, suggesting that autophagy protects the cells from the action of 4-NC. (AU)

• Processo FAPESP: 06/58663-1 - Avaliacao do efeito inibitorio de metaloproteases do extrato de pothomorphe de linhagens de glioma humano.
• Beneficiário: Renato Ramos Massaro
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 06/60930-8 - Pesquisa sistematica de plantas medicinais: potencial farmacoterapeutico de pothomorphe umbellata.
• Beneficiário: Silvia Berlanga de Moraes Barros
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/50915-1 - Efeito da super expressão de gene RECK na reversão do fenótipo invasivo de gliomas
• Beneficiário: Silvya Stuchi Maria-Engler
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/58817-4 - Geração de peles artificiais humanas e melanomas invasivos como plataforma para testes farmacológicos
• Beneficiário: Silvya Stuchi Maria-Engler
• Modalidade de apoio: Auxílio à Pesquisa - Regular