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 micromol 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 kinase 1/2, c-jun N-terminal
kinases and p38; (iv) activation of
NF-kappaB/p65 and
IKK alpha/beta and (v) phosphorylation and degradation of I kappaB alpha. 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.