اثر سلكاكسيب و آلفا توكوفرول در القاي مرگ سلولي در رده ي سلول سرطان

Study of Alpha Tocopherol, Celecoxib Induced Apoptosis in Human Colorectal Carcinoma Cell Line

Background and Objectives: Chronic, unbridled oxidative damages have been known as the culprits behind many chronic diseases, including cancers, atherosclerosis, diabetes and Alzheimerʹs. Cyclooxygenase-2 (COX-2)-the main enzyme involved in inducing these processes- plays an important role in tumor development and progression. COX-2 inhibitors should be used at high doses for a long time in order to bring about chemoprevention and induction of anti-tumor effects. For example, celecoxib prevents colorectal tumor growth and induces apoptosis in both in vitro and in vivo models. Disregulation of COX-2 expression coincides with the development of gastrointestinal malignancy in humans and in animal models of colorectal cancer. Increased COX-2 expression in human colorectal adeno-carcinomas has been elucidated when compared with normal adjacent colonic mucosa. The capacity of vitamin E, particularly in a form, to quench free radical damage, induces apoptosis and impact expression of oncogenes makes it an appropriate choice for chemotherapeutic strategies. Studies have shown that carcinogenesis and DNA damage due to UV are inhibited by vitamin E. The goal of this study was to investigate alpha tocopherol and celecoxib induced apoptosis in human colorectal carcinoma cell line. Methods: In this study, HT29 cells were exposed to different concentrations of tocopherol (5, 10, and 20jiM) and celecoxib (25, 50, 75, IOOjiM) followed by DNA extraction and fragmentation for demonstrating cell death process. Results: The results indicated that celecoxib at lower doses (25, and 50jiM) could not induce cell death, but at higher doses (75, and 100 jiM), DNA fragmentation results typically resembled programmed cell death. Conclusion: ocopherol (5, 10, and 20|iM) in combination with celecoxib improved the impact of celecoxib on cell death induction and made it the rational notion to be combined with vitamin E in clinical practice.