title: Inhibition of beta-catenin and KRAS expressions by Piper betle in azoxymethane-induced colon cancer of male Fischer 344 rats.
abstract: OBJECTIVE
  To investigate the chemopreventive effect of Piper betle (PB) on preneoplastic lesions (aberrant crypt foci [ACF]) induced by azoxymethane (AOM) in rats and its effect on colorectal cancer biomarkers (beta-catenin, KRAS, p53 and p21).
  
  
  METHODS
  A total of 32 male Fischer 344 rats were divided into phase 1 and phase 2 groups (8 and 24 weeks of AOM administration, respectively). Each phase was divided into 4 groups: control or normal saline (NS) (1 mL/kg), AOM (15 mg/kg body weight, once weekly for 2 weeks), PB (75 mg/kg body weight) and AOM + PB. PB was force-fed to rats a week after the second dose of AOM and NS. The colon was cut open longitudinally for methylene blue and immunohistochemistry staining.
  
  
  RESULTS
  AOM administration showed formation of ACF at 8 and 24 weeks. PB, however, did not reduce ACF formation at either week, but it managed to reduce beta-catenin expression and KRAS found highly expressed in the AOM group of phase 1 rats. No immunoreactivities of p53 and p21 were detected in phase 2 rats, but instead inflammatory cells were visible in between the lesions.
  
  
  CONCLUSIONS
  PB may act as a potential chemopreventive agent in the early stage of colon carcinogenesis by suppressing the expressions of beta-catenin and KRAS.
authors.forename: Faezah
authors.initials: F
authors.lastname: Esa
authors.forename: Wan Zurinah Wan
authors.initials: WZ
authors.lastname: Ngah
authors.forename: A Rahman A
authors.initials: AR
authors.lastname: Jamal
authors.forename: Yasmin Anum
authors.initials: YA
authors.lastname: Mohd Yusof
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D008517:Phytotherapy / Q000379:methods*; D031721:Piper betle; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D011916:Rats, Inbred F344; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis*; D018631:ras Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D002273:Carcinogens; C495268:Ctnnb1 protein, rat; C117307:KRAS protein, human; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D001397:Azoxymethane