Chemopreventive activity of lantadenes on two-stage carcinogenesis model in Swiss albino mice: AP-1 (c-jun), NFkappaB (p65) and P53 expression by ELISA and immunohistochemical localization.
Lantadenes are pentacyclic triterpenoids isolated from leaves of Lantana camara L. and have antitumor activity. Lantadene A (LA) and methyl ester of LA (LAM) were earlier studied in the author's lab for their chemopreventive effect on 7,12-dimethylbenz(a)anthracene (DMBA) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced squamous cell carcinoma incidence in Swiss albino mice. The present study was specially designed to initiate the involvement of the molecular targets in chemopreventive activity of these compounds. Skin lesions were induced by twice-weekly topical application of DMBA (100 nmol/100 microl of acetone) for 2 weeks followed by TPA (1.7 nmol/100 microl of acetone) on depilated back of mice for 20 weeks. LA and LAM were administered orally at a dose of 50 mg/kg body weight twice weekly, 1 week before DMBA application and continued for 20 weeks thereafter. A significant decrease in the incidence of number of lesions in mice was obtained in LA/LAM treated groups as compared to DMBA/TPA alone. Significant increase in the protein levels of c-jun, p65, and p53 by ELISA were observed in DMBA/TPA treated mice tumors whereas less expression was observed in LA and LAM treated tumors. Further immunohistochemical localization of transcription factors was studied which also showed less localization of c-jun, p65, and p53 in LA and LAM treated tumors as compared to localization in DMBA/TPA treated tumors. It can be inferred that LA and LAM chemopreventive activity may be linked to the deregulation of above molecular targets which warrants further studies in that direction.
Kaur
Jagdeep
J
Department of Biophysics, Panjab University, Chandigarh, India.
Sharma
Manu
M
Sharma
P D
PD
Bansal
M P
MP
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004952:Esters; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D014018:Tissue Distribution / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004952:Esters; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D009828:Oleanolic Acid; C019074:rehmannic acid