Chemoprotective Effects of Dietary Grape Powder on UVB Radiation-Mediated Skin Carcinogenesis in SKH-1 Hairless Mice

Abstract

Skin cancer is the most frequently diagnosed cancer in the United States, and solar UVR is an established causative factor for approximately 90% of these cases. Despite efforts aimed at UV protection, including use of sunscreen and clothing, annual cases of skin cancer continue to rise. Here, we report that dietary grape powder mitigates UVB-mediated skin carcinogenesis in an SKH-1 hairless mouse model. Using a UVB initiationpromotion protocol, whereby mice were exposed to 180 mJ/cm 2 UVB two times per week for 28 weeks, we determined the effects of a grape powder-fortified diet (3% or 5%) on skin carcinogenesis. Grape powder consumption at both doses resulted in marked inhibition in tumor incidence, as well as a delay in onset of tumorigenesis. Molecular analyses of skin and tumor tissue showed that grape powder-mediated protective response against UVB-induced skin cancer was accompanied by enhanced DNA damage repair, reduced proliferation, increased apoptosis, and modulations in several oxidative stress markers specifically related to inhibition of oxidative stress and increased reactive oxygen species metabolism. NRF2, an activator of cellular antioxidant response, was decreased by grape powder feeding, suggesting a supportive role in tumor cell survival. Overall, our study suggested that dietary grape, containing several antioxidants in natural amalgamation, may protect against UVB-mediated skin carcinogenesis.

Protective Effects of Dietary Grape on UVB-Mediated Cutaneous Damages and Skin Tumorigenesis in SKH-1 Mice

“…After two weeks of GP consumption, 180 mJ/cm 2 UVB was given every other day for 2 weeks ( Figure 1 a). As previously observed [ 24 ], GP supplementation was well tolerated in all mice. The average daily GP consumption in the 5% GP group corresponded to 239.8 ± 11.3 and 197.5 ± 4.1 mg for males and females, respectively.…”

“…Although no registries document the current incidence of NMSC cases in the US, epidemiological studies have reported that cases of NMSC are significantly higher in men than women [ 4 , 5 ]. Previously, we demonstrated the long term effects of GP consumption against UVB-mediated carcinogenesis in female SKH-1 hairless mice [ 24 ]. Here, we sought to determine the effects of GP on UVB skin carcinogenesis in male SKH-1 mice utilizing the same initiation-promotion protocol (180 mJ/cm 2 UVB twice weekly for 28 weeks) ( Figure 2 a), since it is known that males tend to produce larger skin tumors that may appear earlier compared to females, upon UVB exposure [ 31 ].…”

“…The multitude of health benefits related to the biochemistry of grapes suggests that grapes could be useful in preventing skin cancer, especially when used in its whole food form due to the possibility of synergistic activity between the several antioxidant ingredients and other bioactive compounds they contain [ 21 , 22 , 23 ]. Recently, we demonstrated the chemoprotective effects of dietary grape powder (GP) in a long-term UVB-mediated skin tumorigenesis setting in female SKH-1 mice, where we showed that GP supplementation increased DNA damage repair, decreased cell proliferation, and oxidative stress, and increased apoptotic response and ROS metabolism [ 24 ]. However, additional studies in different models and conditions are necessary to validate these findings before embarking on human studies.…”

An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms

“…The diet included a 0, 3, or 5% concentration of freeze-dried GP. The diet resulted in increased apoptosis and reduced lipid peroxidation and proliferative markers [ 220 ]. The treatment also increased NER-facilitated repair of the skin by reducing the level of CPDs [ 220 ].…”

“…The diet resulted in increased apoptosis and reduced lipid peroxidation and proliferative markers [ 220 ]. The treatment also increased NER-facilitated repair of the skin by reducing the level of CPDs [ 220 ]. Overall, grapes and their components exert promising activity as naturally-occurring anti-inflammatory and anti-neoplastic agents.…”