A New Benzo[6,7]oxepino[3,2-b] Pyridine Derivative Induces Apoptosis in Canine Mammary Cancer Cell Lines.

Autor: Jianpraphat N; Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Supsavhad W; Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Ngernmeesri P; Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand., Siripattarapravat K; Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Soontararak S; Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Akrimajirachoote N; Department of Physiology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Phaochoosak N; Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand., Jermnak U; Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand.
Jazyk: angličtina
Zdroj: Animals : an open access journal from MDPI [Animals (Basel)] 2024 Jan 25; Vol. 14 (3). Date of Electronic Publication: 2024 Jan 25.
DOI: 10.3390/ani14030386
Abstrakt: CMC is the most frequently diagnosed cancer and one of the leading causes of death in non-spayed female dogs. Exploring novel therapeutic agents is necessary to increase the survival rate of dogs with CMC. MPOBA is a BZOP derivative that has a significant anticancer effect in a human cell line. The main goal of this study was to investigate the anticancer properties of MPOBA against two CMC cell lines (REM134 and CMGT071020) using a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, a wound healing assay, a transwell migration assay, an Annexin V-FITC apoptosis assay with a flow cytometry analysis, a mRNA expression analysis using quantitative real-time PCR (qRT-PCR), and an immunohistochemistry (IHC). According to the accumulated studies, MPOBA caused significant concentration- and time-dependent reductions in cell proliferation and cell migration and induced apoptosis in both CMC cell lines. In gene expression analysis, nine canine genes, including TP53 , BCL-2 , BAX , epidermal growth factor receptor ( EGFR ), snail transcription factor ( SNAIL ), snail-related zinc-finger transcription factor ( SLUG ), TWIST , E-cadherin , and N-cadherin , were investigated. The mRNA expression results revealed that MPOBA induced upregulation of TP53 and overexpression of the pro-apoptotic gene BAX , together with an inhibition of BCL-2. Moreover, MPOBA also suppressed the mRNA expression levels of SNAIL , EGFR , and N-cadherin and induced upregulation of E-cadherin , crucial genes related to the epithelial-to-mesenchymal transition (EMT). However, there was no significant difference in the IHC results of the expression patterns of vimentin (VT) and cytokeratin (CK) between MPOBA-treated and control CMC cells. In conclusion, the results of the present study suggested that MPOBA exhibited significant anticancer activity by inducing apoptosis in both CMCs via upregulation of TP53 and BAX and downregulation of BCL-2 relative mRNA expression. MPOBA may prove to be a potential candidate drug to be further investigated as a therapeutic agent for CMC.
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje