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Am. J. Biomed. Sci. 2010, 2(1), 79-90; doi: 10.5099/aj100100079
Received: 8 September 2009; | Revised: 1 November 2009; | Accepted:5 December 2009

 

Antitumor Activity of Lantadenes in DMBA/TPA Induced Skin Tumors in Mice: Expression of Transcription Factors

 

Jagdeep Kaur1, Manu Sharma2, P.D. Sharma2 and M.P. Bansal1*

1Department of Biophysics, Panjab University, Chandigarh-160014, India

2University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India

*Corresponding author

M.P. Bansal

Phone: 91-172-2534120

Fax: 91-172-3534118

Email: mpbansal@pu.ac.in

 

Abstract

Various triterpenoids extracted from plants have been shown as chemopreventive agents in cancer. Lantadene A (22β-angeoloxyloxy-3-oxoolean-12-en-28-oic acid; LA) is a pentacyclic triterpenoid, isolated from a weed Lantana camara L. and semisynthetically modified to its methyl ester (Methyl22β-angeoloxyloxy-3-oxoolean-12-en-28-oate; LAM) were used for the present studies. LA and LAM were studied for its chemopreventive effect on 7, 12-dimethylbenz[a]anthracene (DMBA) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced squamous cell carcinoma in Swiss albino mice. The skin lesions were induced by the twice-weekly topical application of DMBA (100nmol/100µl of acetone) for two weeks followed by TPA (1.7nmol/100µl of acetone) on the depilated back of mice. LA and LAM were administered orally at a dose of 50mg/kg body weight twice a week, one week before the topical application of DMBA and continued 20 weeks thereafter. Histopathology of tumors was evaluated in all treatment groups. Previous studies in authors laboratory revealed a significant decrease in incidence and average number of papillomas in mice as compared to DMBA/TPA alone at the end of study. Transcription factors; activator protein-1 (AP-1; c-jun and c-fos), Nuclear factor-kappa B (NF-κB; p65) and p53 were evaluated by using RT-PCR. A significant decrease in the mRNA expression of AP-1 (c-jun and c-fos), NF-κB (p-65) and p53 was observed in LAM and LA treated mice skin tumors. These findings were supported by histopathological studies. From the results, it can be inferred that LAM and LA possesses potential chemopreventive activity and may be linked to the expression of transcription factors.

Keywords:  Lantadene A; Lantadene A methyl ester; AP-1; NF-κB; p53.

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