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

Abstract

Various triterpenoids extd. 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 Me 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 wt. twice a week, one week before the topical application of DMBA and continued 20 wk thereafter. Histopathol. of tumors was evaluated in all treatment groups. Previous studies in authors lab. revealed a significant decrease in incidence and av. no. 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-KB (p-65) and p53 was obsd. in LAM and LA treated mice skin tumors. These findings were supported by histopathol. 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. [on SciFinder(R)]