Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01)
Pinto, Laine Celestino
Mesquita, Felipe Pantoja
Soares, Bruno Moreira
Silva, Emerson Lucena da
Oliveira, Edivaldo Herculano Correa de
Burbano, Rommel Rodriguez
Montenegro, Raquel Carvalho
The objective of study was to examine the role of MBZ on malignant ascites cells and the involvement of C-MYC. Comet assay was used to assess the genotoxic effects of MBZ in AGP01 cells and human lymphocytes; differential staining by ethidium bromide and acridine orange, caspase 3/7 and flow cytometry assay was done to access the mechanisms of apoptosis and cell cycle analysis of MBZ in AGP01 cells. C-MYC amplification, C-MYC mRNA and C-MYC protein expression were evaluated by FISH, RT-qPCR and Western blotting, respectively. In addition, cytotoxicity of MBZ was evaluated in AGP01 and AGP01 shRNA MYC by MTT. MBZ significantly increased the damage index and no produced in human lymphocytes. MBZ caused remarkable cell cycle arrest in G0/G1 and G2/M phases at 0.5μM and 1.0 μM, respectively and induced significantly apoptosis in higher concentrations. Additionally, MBZ (0.5 μM and 1.0 μM) increased caspase 3 and 7 activities. MBZ decreased signals, C-MYC mRNA and C-MYC protein expression in AGP01 cells. MBZ induced lower cell viability in AGP01 cells compared AGP01 shRNA MYC in the same concentration. Therefore, our results show the evidence of C-MYC gene as one of the pathways by which MBZ induces cell death in gastric cancer cells.
xmlui.dri2xhtml.METS-1.0.item-citationPINTO, Laine Celestino et al. Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01). Toxicology in Vitro, v. 60, n. xx, p. 305-312, Oct. 2019.
xmlui.dri2xhtml.METS-1.0.item-decsPrimaryNeoplasias Gástricas / patologia
Genes myc / genética
Mebendazol / efeitos adversos