Evaluation of Caspase 3 as a Target for Apoptosis induced via Chemotherapy in Rats

Background: Apoptosis is a systematic cellular process (programed cell death) that occurs in physiological and pathological conditions. It plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. Caspase 3protein is one of the main executioners of apoptosis. Fluorouracil (5-FU) is a chemotherapeutic agent which has been used against cancer several years ago and now there is uprising interests in its usage as an apoptotic enhancer. Methods: Sixty albino rats were allotted randomly into 2 equal groups, control group I and group II which received intraperitoneal injection of 5-FU. Oral samples (buccal mucosa, gingiva, labial mucosa, tongues and submandibular glands) were routinely processed for Caspase3 immunohistochemical stain. Blood samples were taken from all rats for Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR). Results: A significant loss of weight and oral tissues inflammation has been noticed in group II. This study also revealed a significant difference in the immunostaining of Caspase 3between two groups. Group II had a moderate reaction for Caspase 3in 60% of its samples while the remaining 40% showed an intense reaction. In contrast, group I revealed a mild reaction. Furthermore, the significant increase in group II Caspase 3 expressions was associated with genotype AA which also was associated with genotype heterozygote GT (71% of the tested rats). Conclusion: We concluded that 5-FU injection increases the Caspase protein expressions which enhance the apoptotic activity. Evaluation of Caspase 3 polymorphisms with their haplotypes and amount expression help to define genetic susceptibility to cancer development and response to chemotherapy.