title: Rosmarinic acid inhibits DMH-induced cell proliferation in experimental rats.
abstract: 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.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Karthikkumar
authors.forename: Gunasekaran
authors.initials: G
authors.lastname: Sivagami
authors.forename: Periyasamy
authors.initials: P
authors.lastname: Viswanathan
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Nalini
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D053630:Depsides / Q000494:pharmacology*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000097123:Rosmarinic Acid
chemical_list: D019813:1,2-Dimethylhydrazine; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D000097123:Rosmarinic Acid