ABSTRACT The anticancer efficacy of two different classes of
NSAIDs, the nonspecific
cyclooxygenase (COX) inhibitor
aspirin and the specific
COX-2 inhibitor celecoxib, was examined at their therapeutic anti-inflammatory doses during
1,2-dimethylhydrazine (
DMH)-induced colon
carcinogenesis in a rat model. Eight to 10-week-old male rats of Sprague strain were divided into four groups. While group 1 served as control and received the vehicle of the drugs, groups 2, 3, and 4 were administered freshly prepared
DMH in 1 mM
EDTA saline (pH 7.0) (30 mg/kg
body weight/week, subcutaneously). Groups 3 and 4 were also given a daily treatment of
aspirin (60 mg/kg
body weight, orally) and
celecoxib (6 mg/kg
body weight, orally), respectively, both prepared in carboxy-
methyl cellulose. Animals were sacrificed at the end of 12 weeks and colons from different groups were subjected to macroscopic and histopathological studies, enzymatic activities of
superoxide dismutase (SOD) and
catalase (CAT), and determination of
lipid peroxide level. The maximum number of raised mucosal lesions in proximal, middle, and distal regions of the colon was found in the
DMH group alone, and the lowest number was found in the
celecoxib-treated
DMH group. Histological studies also showed the highest occurrence of dysplastic
aberrant crypt foci (ACF) associated with enlarged lymphoid follicles in all the three portions of colon (i.e., proximal, middle, and distal). The
aspirin-administered
DMH group had lesser ACF in the proximal and middle portions and no ACF in the distal region. The
celecoxib-administered
DMH group showed no ACF in the middle region of the rat colon.
DMH treatment induced lipid peroxidation and inhibited the activities of SOD and CAT. Both the
aspirin- and
celecoxib-treated
DMH groups showed a marked lowering of the
lipid peroxide level along with a significant enhancement of CAT activity when compared with the
DMH-treated group. The results show that
celecoxib was found to be more effective in reducing the ACF occurrence and aggregates of lymphoid tissue than the nonselective COX inhibitor
aspirin, and suggests a possible
chemoprevention modality in
colon cancer. This may have important implications as COX-2 selective drugs at anti-inflammatory doses are better tolerated clinically than standard
NSAIDs, thus making them potentially better chemopreventive agents in
colon cancer.