cyclin-d1 and salvin

This study determined the efficacy of carnosic acid (CA) for suppressing colon carcinogenesis associated with excess adiposity.. 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.. CA appears to alleviate adipocity-related acceleration of colon tumor formation.

Topics: 3T3-L1 Cells; Abietanes; Adipocytes; Adipogenesis; Adiponectin; Adiposity; Animals; Apoptosis; Azoxymethane; bcl-X Protein; Cell Proliferation; Colon; Colonic Neoplasms; Cyclin D1; Dextran Sulfate; Extracellular Signal-Regulated MAP Kinases; HT29 Cells; Humans; Insulin; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Male; Mice; Plant Extracts; Proto-Oncogene Proteins c-akt; Receptor, Insulin; Receptors, Leptin; STAT3 Transcription Factor

The present study has investigated the modulating effect of carnosic acid on the expression pattern of cell proliferative (proliferating cell nuclear antigen (PCNA) cyclin D1 and a transcription factor c-fos), apoptotic (p53, Bcl-2, Bax caspase -3 and 9), inflammatory (Nuclear factor kappa B (NFκB) and cyclooxygenase-2 (COX- 2) and angiogenic (vascular endothelial growth factor (VEGF) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the hamsters buccal pouches by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Hundred per cent tumour formation (well-differentiated squamous cell carcinoma) accompanied by deregulation in the above mentioned molecular markers was noticed in hamsters treated with DMBA alone (tumour bearing hamsters). Oral administration of carnosic acid at dose of 10mg/kg bw to hamsters treated with DMBA not only completely prevented the tumour formation, but also corrected the abnormalities in the expression pattern of molecular markers. The present study suggests that carnosic acid might have inhibited the tumour formation by exerting anti-cell-proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Abietanes; Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Biomarkers; Carcinogenesis; Carcinoma, Squamous Cell; Cell Proliferation; Cyclin D1; Inflammation Mediators; Male; Mesocricetus; Mouth Neoplasms; Phytotherapy; Plant Extracts; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-fos; Rosmarinus; Vascular Endothelial Growth Factor A