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| Am. J. Biomed. Sci. 2010, 2(1), 79-90; doi: 10.5099/aj100100079 |
Antitumor Activity of Lantadenes in
DMBA/TPA Induced Skin Tumors in Mice: Expression of Transcription Factors |
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Jagdeep Kaur1, Manu Sharma2, P.D. Sharma2
and M.P. Bansal1* |
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1Department of Biophysics, |
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2University Institute of Pharmaceutical Sciences, |
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*Corresponding author |
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M.P.
Bansal |
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Phone:
91-172-2534120 |
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Fax:
91-172-3534118 |
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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. Download the full article (PDF)
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