Rosmarinic acid inhibits DMH-induced cell proliferation in experimental rats.

Background: Colon cancer is one of the most common cancers in both men and women. The present study is an effort to unravel the anticarcinogenic effects of rosmarinic acid (RA) in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Administration of DMH induces multiple tumors in the rat colon, which mimics human colon cancer.

Methods: Male Wistar rats were divided into six groups and fed a high-fat diet. Group 1 served as control, group 2 rats were given RA [5 mg/kg body weight (b.w.)] orally every day for a total period of 30 weeks, and groups 3-6 were given weekly injections of DMH (20 mg/kg b.w. subcutaneous) once a week in the groin for the first 15 weeks. In addition to DMH, groups 4-6 received RA at a dose of 5 mg/kg b.w. during the initiation and postinitiation stages, and also throughout the entire study period. Colon tissues were examined histologically; further, the extent of oxidative stress was assessed by measuring lipid peroxidation and antioxidant levels in the colonic mucosa of rats.

Results: Macroscopic and microscopic tumors were identified in all the groups that received DMH. The results revealed that supplementation with RA significantly inhibited the tumor formation and tumor multiplicity in DMH-treated rats. RA supplementation to DMH-administered rats significantly reduced the cell proliferation markers, namely, argyrophilic nucleolar organizing regions as well as proliferative cell nuclear antigen labeling index. In addition, RA supplementation reduces the expressions of tumor necrosis factor-α, interlukin-6, and cyclooxygenase-2, and modulates the expression of p65.

Conclusions: The above findings clearly underline the chemopreventive efficacy of RA against DMH-induced colon carcinogenesis.