Syed, D.N., Afaq, F., Mukhtar, H. University of Wisconsin, Madison, WI, USA.

This study by researchers in the University of Wisconsin’s Dept. of Dermatology used MatTek’s EpiDermFT full-thickness in vitro 3-D human skin tissue equivalent because it “sustains differentiation and exhibits morphological and metabolic properties similar to human skin”, to demonstrate the effect of a test substance applied to EpiDerm-FT to prevent skin cancer. Because treatment options for advanced metastasized cancers remain inadequate, developing effective approaches for the prevention of cancer has become an important goal to reduce cancer burden. One such strategy is through chemo-prevention, preferably by the use of non-toxic dietary substances and botanical products. Pomegranate, used for centuries for its medicinal properties, is now being recognized as a potential chemopreventive and anticancer agent. Increasing body of evidence has underscored the cancer preventive efficacy of pomegranate both in vitro and in vivo animal models. The emerging data provide new insights into the molecular framework needed to establish novel mechanism-based chemopreventive strategies for various human cancers. Pomegranate and Skin Cancer: Pomegranate Against Photocarcinogenesis: EpiDermFT-Related Studies: Solar UV radiation is known to accelerate aging changes, causing fine and coarse wrinkling, rough skin texture, dryness, telangiectasia and dyspigmentation. The individual effect of pomegranate juice, oil, and byproduct was determined against UVB-mediated damage using reconstituted human skin EpiDermFT™ 200, which sustains differentiation and exhibits morphological and metabolic properties similar to human skin. Pretreatment of EpiDermFT with juice, oil or byproduct resulted in marked inhibition in the number of cyclobutane primidine dimers (CPDs) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) positive cells, reflecting a protective effect of these compounds against UVB-mediated DNA damage. In addition, downregulation of UVB-induced increase in PCNA protein expression and an increase in p21/WAF1 expression in pomegranate treated cells indicates that inhibition of cell proliferation could be one of the mechanisms by which pomegranate protects damaged cells from entering the cell cycle, thereby affording these cells additional time for DNA damage repair and avoid replication error that otherwise often results in carcinogenic mutation. Characteristic dyskeratotic sunburn cells with pyknotic nuclei detected in UVB-irradiated EpiDermFT were markedly decreased in EpiDermFT pretreated with pomegranate components prior to UVB irradiation. UVB irradiation results in the induction of a series of matrix metalloproteinases (MMPs) which degrade collagen, elastin and other extracellular matrix proteins and eventually cause skin wrinkling. It was shown that all three components of pomegranate were able to inhibit UVB-induced expressions of MMPs (-1,-2,-3,-7,-8,-9,-11,-12) as well as MMP-2 and MMP-9 activity in the EpiDermFT. Decreased procollagen expression is partly mediated by c-Jun, which is induced by UV light and interferes with procollagen transcription. Pretreatment of EpiDermFT with pomegranate derived products inhibited UVB-induced phosphorylation of c-Jun and increased protein expression of c-Fos. In addition, inhibition of UVB-mediated increase in tropoelastin, the major protein component of elastic fibers by these products is indicative of their usefulness against UVB-induced damage to human skin.


8-hydroxyl-2’-deoxyguanosine (8-OHdG), Apoptosis, Cell proliferation, Chemoprevention, Cyclobutane primidine dimers (CPDs), Dyskeratotic sunburn cells, EpiDerm-FT, EpiDermFT, MMP-1, MMP-11, MMP-12, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, Metalloproteinases (MMPs), PCNA protein, Pomegranate, Pyknotic nuclei, Tropoelastin, c-Jun

Materials Tested

Pomegranate derived products, Pomegranate juice, Pomegranate oil, UVB

Request a copy of this paper, click here.