Pomegranate Extract & Chemoprevention

Pomegranate fruit extract could be a novel agent for cancer chemoprevention: Studies in mouse skin

Farrukh Afaq, Mohammad Saleem, Richard Brans, Hasan Mukhtar.

University of Wisconsin, Madison, WI.

Pomegranate fruit extract (PFE) derived from the tree Punica granatum has been extensively used as a folk medicine by many cultures.

PFE contains several polyphenols (such as catechins, gallic and ellagic acids) and anthocyanidins (such as delphinidin, cyanidin, and pelargonidin) and its antioxidant activity, though varies depending upon the variety, is higher than that of red wine and green tea.

In the present study, we evaluated whether PFE could possesses anti-tumor promoting effects. We determined the effect of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase (ODC) and cyclooxygenase-2 (COX-2) activities and protein expression, edema and hyperplasia, the conventional markers, and other markers of skin tumor promotion.

We found that topical application of PFE (1 mg/mouse) 30 min prior to TPA (3.2 n mole/mouse) application onto the skin of CD1 mice afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in skin edema and hyperplasia.

Topical application of PFE was also found to result in substantial inhibition against TPA-induced epidermal ODC activity and protein expressions of ODC and COX-2. Mitogen activated protein kinase (MAPK) belongs to a family of serine/threonine protein kinases, including extracellular-signal-regulated protein kinases (ERK1/2), p38 kinase and c-Jun terminal kinases (JNKs).

Because of the role of MAPK in inflammatory responses, cell growth, proliferation, survival and apoptosis, we next assessed the effect of PFE on TPA-mediated activation of MAPK pathway in mouse epidermis.

Employing Western blot analysis and immunohistochemistry, we found that topical application of PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, JNKs, and p38 in the epidermis. Since the nuclear factor kappa B (NF-êB) has been implicated in cellular proliferation and tumor promotion, we next determined the effect of PFE on TPA-mediated activation of NF-êB pathway.

Our data showed that pre-application of PFE to mouse skin significantly inhibited TPA-induced activation of NF-êB, IKKá, and degradation of IêBá.

The results of our study, for the first time, provide suggestion that PFE could be a useful anti-tumor promoting agent in mouse skin.

Because PFE is capable of inhibiting several biomarkers of TPA-induced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models.

AACR Abstract Number: 4783, 2003


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