Chemopreventive effects of NSAIDs as inhibitors of cyclooxygenase-2 and inducers of apoptosis in experimental lung carcinogenesis

Abstract

Roles of cyclooxygenase (COX) enzyme and intrinsic pathway of apoptosis have been explored for the chemopreventive effects of non-steroidal anti-inflammatory drugs (NSAIDs) on 9,10-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat model. 16 weeks after the administration of DMBA, morphological analysis revealed the occurrences of tumours and lesions, which were regressed considerably with the co-administration of indomethacin and etoricoxib, the two NSAIDs under investigation. DMBA group was marked by hyperplasia and dysplasia as observed by histological examination, and these features were corrected to a large extent by the two NSAIDs. Elevated levels of COX-2 were seen in the DMBA group, the enzyme responsible for prostaglandin synthesis during inflammation and cancer, whilst the expression of the constitutive isoform, COX-1, was equally expressed in all the groups. Apoptosis was quantified by studying the activities of apaf-1, caspase-9, and 3 by immunofluorescence and western blots. Their activities were found to diminish in the DMBA-treated animals as compared to the other groups. Fluorescent co-staining of the isolated broncho-alveolar lavage cells showed reduced number of apoptotic cells in the DMBA group, indicating decrease in apoptosis after carcinogen administration. The present results thus suggest that the mechanism of cancer chemoprevention of NSAIDs may include the suppression of COX-2 and the induction of apoptosis.

Celecoxib prevents colitis associated colon carcinogenesis: An upregulation of apoptosis

“…Protein extracted from 10% tissue homogenate was used to study the expression of cell cycle regulators and apoptotic proteins by immunoblotting. These methods have been described in detail in earlier publications from this laboratory [16,17].…”

Benefits of the antioxidant and anti‐inflammatory activity of etoricoxib in the prevention of ovarian ischemia/reperfusion injury induced experimentally in rats

“…The COX enzyme has two well‐known isoforms. One, the COX‐1 isoform, is involved in the production of cytoprotective prostaglandin in tissues and in tissue hemostasis . The COX‐2 isoform is inducible and is involved in the production of inflammation mediators in damaged tissues.…”

Indometacin Ameliorates High Glucose-Induced Proliferation and Invasion Via Modulation of E-Cadherin in Pancreatic Cancer Cells

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