Journal Article

Guggulsterone modulates MAPK and NF-κB pathways and inhibits skin tumorigenesis in SENCAR mice

Sami Sarfaraz, Imtiaz A. Siddiqui, Deeba N. Syed, Farrukh Afaq and Hasan Mukhtar

in Carcinogenesis

Volume 29, issue 10, pages 2011-2018
Published in print October 2008 | ISSN: 0143-3334
Published online August 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn180
Guggulsterone modulates MAPK and NF-κB pathways and inhibits skin tumorigenesis in SENCAR mice

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Guggulsterone (GUG), a resin of the Commiphora mukul tree, has been used in ayurvedic medicine for centuries to treat a variety of ailments. Recent studies have suggested that GUG may also possess anticancer effects. In the present study, we show that GUG possesses antitumor-promoting effects in SENCAR mouse skin tumorigenesis model. We first determined the effect of topical application of GUG to mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of GUG (1.6 μmol per mouse) 30 min prior to TPA (3.2 nmol per mouse) application onto the skin of mice afforded significant inhibition against TPA-mediated increase in skin edema and hyperplasia. Topical application of GUG was also found to result in substantial inhibition against TPA-induced epidermal (i) ornithine decarboxylase (ODC) activity; (ii) ODC, cyclooxygenase-2 and inducible nitric oxide synthase protein expressions; (iii) phosphorylation of extracellular signal-regulated kinase1/2, c-jun N-terminal kinases and p38; (iv) activation of NF-κB/p65 and IKKα/β and (v) phosphorylation and degradation of IκBα. We next assessed the effect of topically applied GUG on TPA-induced skin tumor promotion in 7,12-dimethyl benz[a]anthracene-initiated mice. Compared with non-GUG-pretreated mice, animals pretreated with GUG showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance from 5 to 11 weeks. These results provide the first evidence that GUG possesses anti-skin tumor-promoting effects in SENCAR mice and inhibits conventional as well as novel biomarkers of tumor promotion. In summary, GUG could be useful for delaying tumor growth in humans.

Journal Article.  6423 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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