title: Carnosic acid suppresses colon tumor formation in association with antiadipogenic activity.
abstract: METHODS
  This study determined the efficacy of carnosic acid (CA) for suppressing colon carcinogenesis associated with excess adiposity.
  
  
  RESULTS
  Cell growth regulation by CA was evaluated in HT-29 colon adenocarcinoma cells cocultured with 3T3-L1 adipocytes. To determine the in vivo efficacies, male A/J mice were divided into four groups and fed one of the following experimental diets for 11 wk: 15% fat, 45% fat, 45% fat + 0.01% CA, or 45% fat + 0.02% CA. Azoxymethane was administered at the beginning of experimental diet and two cycles of dextran sodium sulfate were supplied 1 wk after the azoxymethane injection. The proliferation of HT-29 cells cocultured with 3T3-L1 cells was significantly higher than proliferation of control cells (p < 0.05). CA treatment suppressed the growth of cocultured HT-29 cells through cell cycle arrest and enhanced apoptosis by inhibiting leptin receptor (Ob-R) signaling, including Akt and extracellular signal-regulated kinase (ERK) phosphorylation. CA supplementation in vivo decreased the number of colon tumors and reduced circulating concentrations of leptin, adiponectin, insulin, and insulin-like growth factor 1. Colonic expression of Ob-R, insulin receptor (IR), p-Akt, p-ERK, B-cell lymphoma extra large (Bcl-xL), and cyclinD1 protein was also suppressed in animals fed CA.
  
  
  CONCLUSIONS
  CA appears to alleviate adipocity-related acceleration of colon tumor formation.
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
authors.forename: Yun-Ji
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Kim
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Seo
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Sung
mesh_terms: D041721:3T3-L1 Cells; D045784:Abietanes / Q000494:pharmacology*; D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000097:blood; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000009:adverse effects; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D052242:Adiponectin; C494812:Bcl2l1 protein, mouse; C530105:Ccnd1 protein, mouse; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D010936:Plant Extracts; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051020:bcl-X Protein; C515447:leptin receptor, mouse; D019938:Cyclin D1; D007334:Insulin-Like Growth Factor I; D016264:Dextran Sulfate; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C018381:salvin; D001397:Azoxymethane
keywords: Carnosic acid; Colitis; Colon cancer; Obesity