Anticancer effects of dibenzo[b,f]oxepine derivatives on canine mammary cancer cell lines

Name: Natamon Jianpraphat

LCSH: Kasetsart University -- Theses. M.S. (Veterinary Pharmacology and Toxicology) 2023

Classification :.LCCS: SF992.C35

LCSH: Kasetsart University. Department of Veterinary Pharmacology -- Theses

LCSH: Dogs -- Diseases

LCSH: Cancer in animals

LCSH: Antineoplastic agents

LCSH: Veterinary oncology

Abstract: Canine mammary cancers (CMCs) are 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. 2-((2-methylpyridin-3-yl)oxy)benzaldehyde (MPOBA) is a benzo[6,7]oxepino[3,2- b]pyridine (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, canine mammary carcinoma (REM134) and canine mammary tubulopapillary carcinoma (CMGT071020) using 3-(4,5-Dimethyl2-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, mRNA expression analysis using quantitative real‐time PCR (qRT-PCR), and immunohistochemistry (IHC). According to the accumulated studies, MPOBA caused significant concentration- and time-dependent reductions in cell proliferation, cell migration, and it was able to induce apoptosis in both CMC cell lines. In gene expression analysis, nine canine genes including tumor protein 53 (TP53), B-cell lymphoma 2 (BCL-2), Bcl-2-associated X (BAX), epidermal growth factor receptor (EGFR), snail transcription factor (SNAIL), snail-related zinc-finger transcription factor (SLUG), twist family BHLH transcription factor (TWIST), Ecadherin, 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, 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 IHC results of the expression pattern 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 be a potential candidate drug to be further investigated as a therapeutic agent for CMCs.

Kasetsart University. Office of the University Library

Address: Bangkok

Email: tdckulib@ku.ac.th

Name: Usuma Jermnak

Role: Thesis Advisor

Name: Wachiraphan Supsavhad

Role: Thesis Co-Advisor

Created: 2023

Modified: 2025-06-24

Issued: 2025-06-24

วิทยานิพนธ์/Thesis

application/pdf

URL: http://www.lib.ku.ac.th/KUthesis/2566/natamon-jian-all.pdf

CallNumber: SF992.C35.N391

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Veterinary Pharmacology and Toxicology

Grantor: Kasetsart University

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