Anti-Cancer Acitivity of Etodolac and Its Derivatives on Prostate and Colorectal Cancer Cell Lines

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as anti-inflammatory and analgesic agents. This family of drugs suppresses prostaglandin synthesis through inhibition of cyclooxygenase (COX) enzymes. Recent studies showed that anti-carcinogenic effects of these drugs are especially mediated by COX-2 enzyme. Etodolac is a COX-2 inhibitor and though not perfectly selective, it exhibits “preferential selectivity„ for COX-2. In this study, the anti-proliferative and apoptotic effects of etodolac and its hydrazone or triazole derivatives (SGK 206 and SGK 242, respectively), were investigated on prostate cancer cell line PC-3 and human colorectal carcinoma cell line HT-29. Our data showed that SGK 206 and SGK 242 were more effective in the inhibition of proliferation and induction of apoptosis compared to etodolac in both cell lines

Effect of etodolac hydrazone, a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity

The aim of this study was to investigate the effect of etodolac hydrazone (EH), a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity in rats. Group 1 (n = 8) received 1 ml dimethyl sulfoxide (DMSO) daily (Control); group 2 (n = 8) was treated with 5 mg kg 1 day 1 EH, dissolved in 1 ml DMSO (EH- 5); and group 3 (n = 8) was treated with 10 mg kg 1 day 1 EH, dissolved in 1 ml DMSO (EH-10). All administrations were performed by gavage and maintained for 8 weeks. Both doses of EH administration caused significant decreases in absolute and relative weights of testis, whole epididymis, right cauda epididymis, and spermatozoon motility, spermatozoon count in comparison with the control group. Only 10 mg kg 1 day 1 EH administration caused significant decreases in absolute and relative weights of seminal vesicles and serum testosterone level, and significant increases in testicular lipid peroxidation level, and numbers of TUNEL+ apoptotic germ cells and spermatozoa with damaged DNA along with some histopathological damages when compared to the control group. However, body and ventral prostate weight, and testicular antioxidant markers (glutathione, glutathione-peroxidase and catalase), were unaffected significantly by both doses of EH administration. In conclusion, two different doses of EH, in particular its high dose, damage to testicular spermatogenic cells and spermatozoon DNA and, it decreases spermatozoon motility, count and testosterone level in healthy rats