Journal
CANCERS
Volume 12, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/cancers12071751
Keywords
non-melanoma skin cancer; grape; SKH-1; UVB; chemoprevention
Categories
Funding
- California Table Grape Commission
- National Institutes for Health [R01AR059130, R01CA176748]
- Department of Veterans Affairs [I01CX001441, I01BX004221, IK6BX003780]
- Skin Diseases Research Center (SDRC) from NIH/NIAMS [P30AR066524]
- UW Department of Pathology and Laboratory Medicine, UWCCC [P30 CA014520]
- Office of The Director-NIH [S10OD023526]
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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.
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