Abstract
Non-melanoma skin cancers (NMSCs) are the most diagnosed cancers in the US and occur more frequently in males. We previously demonstrated chemoprotective effects of dietary grape powder (GP) against UVB-mediated skin tumorigenesis in female SKH-1 mice. To expand on this, here, we determined the effects of GP in a short-term UVB exposure protocol (0 or 5% GP, followed by UVB every other day for 2 weeks) in male and female SKH-1 mice, as well as explored any sex-related differences in UVB carcinogenesis via male SKH-1 mice (0, 3, or 5% GP; UVB twice weekly for 28 weeks). In the short-term study, we found that GP protects against early-stage epithelial hyperplasia and mast cell infiltration in both sexes. In the long term, GP markedly reduced tumor counts and malignant conversion, along with significant decreases in mast cell infiltration, serum IgE and Eotaxin. We also found inhibition of P38 phosphorylation and reduced PCNA, Ki67 and BCL2 levels, suggesting that the anti-inflammatory effects of GP inhibits P38, acting as an upstream regulator to inhibit proliferation and reduce tumor cell survival. Together, GP appears to protect against UVB-mediated skin damage and carcinogenesis in SKH-1 mice and should be explored further as a supplement for NMSC prevention.
Highlights
Non-melanoma skin cancers (NMSCs) are the most frequently diagnosed cancer, affecting more than 3.5 million Americans annually [1]
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 reactive oxygen species (ROS)
Upon evaluation of upstream regulators of acute phase response (APR) in the female mice, including ERK1/2 and nuclear factor-κB (NF-κB), we found that anti-inflammatory effects of GP were associated with modulation in these pathways leading to inhibition of tumor growth [37]
Summary
Non-melanoma skin cancers (NMSCs) are the most frequently diagnosed cancer, affecting more than 3.5 million Americans annually [1]. The rising incidence of skin cancer diagnoses suggests a need for additional strategies for NMSC management One such approach is chemoprevention with dietary antioxidants, such as grape antioxidant resveratrol, which has been extensively studied for its health and benefits and chemopreventive effects [19,20]. 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]. Employing a long-term UVB protocol of skin carcinogenesis, we determined the effect of GP feeding on NMSC formation in male SKH-1 hairless mice to determine any possible biological variability in the observed responses due to sex
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