Abstract 5263: Chemopreventive effects of dietary grapes on skin cancer
Authors: Singh Chandra K. , Ndiaye Mary A. , Mintie Charlotte A. , Chhabra Gagan , Ahmad Nihal 
Published: July 2017

Abstract
Non-melanoma skin cancer (NMSC) is the most commonly diagnosed malignancy in the United States, affecting more than 3 million Americans each year. Ultraviolet (UV) radiation from the sun, particularly its UVB component (290-320 nm), is an established causative factor for ~90% of skin cancers. The two most common forms of skin cancer, basal- and squamous- cell carcinomas, are treatable if detected early. However, they can be difficult to treat and potentially fatal if left until late stages. Further, epidemiological studies have suggested an amplified risk of other deadly cancers in individuals with a history of skin cancer. Therefore, it is important to design novel approaches, especially focusing on prevention, for the management of skin cancers. Studies from our laboratory and by others have shown that topical application of the grape antioxidant resveratrol possesses promise in the prevention of skin cancer. However, ideally cancer preventive agents need to be orally administrable for ease of use and broader human acceptability. With this in mind, in this study, we determined the efficacy of dietary grape powder (containing resveratrol in natural amalgamation with catechins, anthocyanins, polyphenols and flavonols) against UVB-mediated skin tumorigenesis in the SKH-1 hairless mouse model, which is regarded to have relevance to human NMSC. We employed a UVB initiation-promotion protocol in which the mice were subjected to chronic UVB exposure (180 mJ/cm2; twice weekly, for 28 weeks). The animals received either AIN-76A or grape powder (GP) fortified diet (3% and 5% GP, obtained from the California Table Grape Commission), all of which were sugar-matched to the highest GP content. Our data demonstrated that the consumption of GP at both 3% and 5% resulted in a significant inhibition in skin tumor incidence and delay in the onset of tumorigenesis. The average consumption of feed per mouse was 3.5 g/day, corresponding to 105 and 174 mg GP/day in the 3% and 5% GP treatment groups. This dosing regimen seems to be easily achievable for human consumption, as it corresponds to 25.5 and 42.4 g/day, which are equivalent to 1.1 and 1.8 serving of fresh grapes, respectively. Our data also demonstrated that the observed skin cancer chemopreventive effects of grape powder were accompanied by significant i) decreases in cellular proliferation markers Ki67 and PCNA, ii) decreases in the oxidative stress marker 4-HNE, and iii) increases in the levels of cleaved caspase 7 and poly (ADP-ribose) polymerase (PARP). Interestingly, NRF2, an activator of cellular antioxidant response, was found to be downregulated in GP treated tumors, compared to UVB alone groups, suggesting a potential protective role of NRF2 in the survival of tumor cells. Overall, our study suggests a strong chemopreventive effect of dietary grape and provides a basis for future human studies.
Citation Format: Chandra K. Singh, Mary A. Ndiaye, Charlotte A. Mintie, Gagan Chhabra, Nihal Ahmad. Chemopreventive effects of dietary grapes on skin cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5263. doi:10.1158/1538-7445.AM2017-5263