title: Chlorophyllin abrogates canonical Wnt/β-catenin signaling and angiogenesis to inhibit the development of DMBA-induced hamster cheek pouch carcinomas.
abstract: BACKGROUND
  Chlorophyllin, a water soluble semi-synthetic food-grade derivative is reported to exhibit a wide range of beneficial health effects. We investigated the effect of chlorophyllin supplementation on Wnt/β-catenin and vascular endothelial growth factor (VEGF) signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model.
  
  
  RESULTS
  Hamsters were divided into 4 groups. The right buccal pouches of group 1 and 2 hamsters were painted with 0.5 % DMBA for 14 weeks. Group 2 animals received in addition chlorophyllin (4 mg/kg bw) in the diet. Group 3 animals received chlorophyllin alone and group 4 animals served as control. mRNA and protein expression of components of Wnt, VEGF, and PI3K/Akt signaling pathways were analyzed by RT-PCR and Western blot analysis. Dietary chlorophyllin administration suppressed the development of HBP carcinomas by altering the expression of several components of the Wnt/β-catenin signaling pathway. This was associated with inhibition of angiogenesis as evidenced by decreased expression of the proangiogenic factors HIF-1α, VEGF, and VEGFR2. Chlorophyllin administration also downregulated the expression of histone deacetylases involved in epigenetic regulation of tumor angiogenesis.
  
  
  CONCLUSIONS
  Dietary chlorophyllin that abrogates Wnt/β-catenin and VEGF signaling by targeting a multitude of key signaling molecules is an attractive candidate for preventing tumor progression.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India. snlabau@gmail.com
authors.forename: Siddavaram
authors.initials: S
authors.lastname: Nagini
authors.forename: Nagini
authors.initials: N
authors.lastname: Siddavaram
authors.forename: Ramamurthi
authors.initials: R
authors.lastname: Vidya Priyadarsini
authors.forename: Vidya Priyadarsini
authors.initials: VP
authors.lastname: Ramamurthi
authors.forename: Veeran
authors.initials: V
authors.lastname: Veeravarmal
authors.forename: Veeravarmal
authors.initials: V
authors.lastname: Veeran
authors.forename: Rajakishore
authors.initials: R
authors.lastname: Mishra
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015153:Blotting, Western; D002610:Cheek / Q000473:pathology*; D002735:Chlorophyllides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006655:Histone Deacetylases / Q000378:metabolism; D008297:Male; D009062:Mouth Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002735:Chlorophyllides; D012333:RNA, Messenger; D051176:beta Catenin; D015127:9,10-Dimethyl-1,2-benzanthracene; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D006655:Histone Deacetylases; C007020:chlorophyllin