Skin cancer is the most common human cancer and the number one cancer in terms of incidence in the USA. Ultraviolet (UV) irradiation in solar light elicits various biological responses in the skin, including inflammation, pigmentation, erythema, and cell death, and therefore the role of UV light as a major etiologic factor is of particular concern. The use of sunscreens or sun blocks has not been effective in preventing skin cancer, and therefore new mechanism-based approaches are critically needed to treat UV-induced skin cancer. This project is aimed toward investigating the role of leukotriene A4 hydrolase (LTA4H) in solar ultraviolet (UV) - induced skin carcinogenesis. LTA4H was shown to exhibit high levels of protein expression in certain types of cancers and its inhibition leads to a reduced cancer incidence in various animal models. Importantly, our preliminary data indicate that suppressing LTA4H expression and activity decreases skin carcinogenesis in the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) two-stage mouse skin carcinogenesis model. We also reported that [6]-gingerol or resveratrol binds with LTA4H to suppress colon or pancreatic cancer cell growth, respectively, in vivo. We hypothesize that inhibition of LTA4H by [6]-gingerol or resveratrol will result in suppression of solar UV-induced skin carcinogenesis.

Public Health Relevance

Skin cancer is the most common human cancer and the number one cancer in terms of incidence in the USA. The use of sunscreens or sun blocks has not been effective in preventing skin cancer, and therefore new mechanism-based approaches are critically needed to treat UV-induced skin cancer. Leukotriene A4 hydrolase (LTA4H) was shown to exhibit high levels of protein expression in certain types of cancers, including skin cancer, and its inhibition leads to a reduced cancer incidence. We hypothesize that inhibition of LTA4H by [6]- gingerol or resveratrol will result in suppression of solar UV-induced skin carcinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA196639-04
Application #
9512880
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Ross, Sharon A
Project Start
2015-07-22
Project End
2020-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biochemistry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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