Toxicology in vitro, 2019-10, Vol.60, p.305-312
2019
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- Autor(en) / Beteiligte
- Titel
- Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01)
- Ist Teil von
- Toxicology in vitro, 2019-10, Vol.60, p.305-312
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. Graphical abstract [Display omitted] •MBZ causes DNA damage in AGP-01 cells and it is not causes in human lymphocytes.•MBZ cell cycle arrest in G2/M in the higher concentration in AGP-01 cells.•MBZ induces apoptosis and increases caspase 3 and 7 activities in AGP-01 cells.•MBZ decreases signals of MYC amplification in AGP-01 cells.•MBZ decreases MYC mRNA expression and MYC protein expression in AGP-01 cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0887-2333eISSN: 1879-3177DOI: 10.1016/j.tiv.2019.06.010Titel-ID: cdi_proquest_miscellaneous_2242816489
- Format
- –
- Schlagworte
- Acridine orange, Apoptosis, Apoptosis - drug effects, Ascites, Ascites - drug therapy, Ascites - genetics, Ascites - metabolism, Ascites cells, Bioassays, C-MYC, c-Myc protein, Caspase, Caspase-3, Cell cycle, Cell Cycle - drug effects, Cell death, Cell Line, Tumor, Cell Survival - drug effects, Cell viability, Comet assay, Cytotoxicity, Damage, Damage detection, Deactivation, DNA Damage, Drug target, Ethidium bromide, Flow cytometry, Gastric cancer, Gene expression, Genotoxicity, Humans, Inactivation, Lymphocytes, Lymphocytes - drug effects, Mebendazole, Mebendazole - pharmacology, mRNA, Myc protein, Protein expression, Proteins, Proto-Oncogene Proteins c-myc - genetics, Proto-Oncogene Proteins c-myc - metabolism, Stomach Neoplasms - drug therapy, Stomach Neoplasms - genetics, Stomach Neoplasms - metabolism, Toxicity, Tubulin Modulators - pharmacology, Western blotting