Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

• Published in: Brazilian journal of medical and biological research Vol. 47; no. 1; pp. 50 - 59
• Main Authors: Sakane, K K, Monteiro, C J, Silva, W, Silva, A R, Santos, P M, Lima, K F, Moraes, K C M
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01-01-2014; Associação Brasileira de Divulgação Científica
• Subjects: Analysis; Animals; BIOLOGY; Biomedical Sciences; Blotting, Western; Cardiovascular diseases; Causes of; Celecoxib; Cell death; Cell Line; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell Survival - drug effects; Cell Survival - genetics; Cellular and molecular analyses; COX-2 inhibitors; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2 inhibitor; Dosage and administration; Dose-Response Relationship, Drug; Drug therapy; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; H9c2 cardiac cell line; MEDICINE, RESEARCH & EXPERIMENTAL; Myoblasts, Cardiac - drug effects; Pyrazoles - pharmacology; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - drug effects; RNA, Messenger - genetics; Spectroscopy, Near-Infrared; Sulfonamides - pharmacology; Time Factors; Cyclooxygenase-2 inhibitor; H9c2 cardiac cell line; Cell death; Cellular and molecular analyses
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X20133028

Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.