The primary goal of the proposed supplement is to determine the mechanism by which dietary supplementation with a vitamin E derivative protects against UVB-induced skin cancer, which is within the scope of the parent grant. The incidence of skin cancer, the most common cancer in the US, continues to rise at an alarming rate. One major risk factor is UVB radiation in sunlight, causing DNA damage and subsequent tumorigenic mutations. These UVB-induced DNA damage products across the genome are repaired by the global genome NER (GG-NER) machinery. Functional GG-NER is essential for preventing mutations and skin tumorigenesis. One of the potential effective strategies for preventing skin cancer is enhancing GG-NER through dietary supplementation with a vitamin E derivative. However, its mechanism of action remains poorly understood. Recently, we discovered a novel role for vitamin E derivative in enhancing GG-NER. Guided by our preliminary data, we hypothesize that this dietary supplement enhances GG-NER and thus inhibits UVB- induced skin cancer. Our hypothesis will be tested in two Specific Aims.
Aim 1 will determine the mechanism by which the vitamin E derivative regulates GG-NER.
Aim 2 will determine the mechanism by which the vitamin E derivative affects UVB-induced skin tumorigenesis in mice. Successful completion of our proposed project will vastly expand our knowledge of the mechanism of action of the vitamin E derivative in GG-NER and skin cancer, and may provide new opportunities for developing better strategies to prevent and treat skin cancer using dietary supplement vitamin E derivative. Since GG-NER is critical for tumor suppression in the skin, lungs, and brain 18, our work here in GG-NER regulation by the vitamin E derivative may not only be significant for skin cancer, but may also be applicable to other tumor types as well.

Public Health Relevance

Skin cancer is the most common cancer. Preventing skin cancer by dietary vitamin E derivative supplementation is a potentially effective approach. Our proposed work will elucidate a new molecular mechanism in preventing skin tumorigenesis by dietary vitamin E derivative supplementation and will provide proof-of-principle evidence for targeted skin cancer prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
3R01ES024373-05S1
Application #
9791591
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Humble, Michael C
Project Start
2015-05-01
Project End
2020-04-30
Budget Start
2019-07-15
Budget End
2020-04-30
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Robinson, Myles; Shah, Palak; Cui, Yan-Hong et al. (2018) The Role of Dynamic m6 A RNA Methylation in Photobiology. Photochem Photobiol :
Sample, Ashley; He, Yu-Ying (2018) Mechanisms and prevention of UV-induced melanoma. Photodermatol Photoimmunol Photomed 34:13-24
Shah, Palak; Zhao, Baozhong; Qiang, Lei et al. (2018) Phosphorylation of xeroderma pigmentosum group C regulates ultraviolet-induced DNA damage repair. Nucleic Acids Res 46:5050-5060
Sample, Ashley; Zhao, Baozhong; Wu, Chunli et al. (2018) The Autophagy Receptor Adaptor p62 is Up-regulated by UVA Radiation in Melanocytes and in Melanoma Cells. Photochem Photobiol 94:432-437
Zhao, Baozhong; Shah, Palak; Qiang, Lei et al. (2017) Distinct Role of Sesn2 in Response to UVB-Induced DNA Damage and UVA-Induced Oxidative Stress in Melanocytes. Photochem Photobiol 93:375-381
Yang, Seungwon; Qiang, Lei; Sample, Ashley et al. (2017) NF-?B Signaling Activation Induced by Chloroquine Requires Autophagosome, p62 Protein, and c-Jun N-terminal Kinase (JNK) Signaling and Promotes Tumor Cell Resistance. J Biol Chem 292:3379-3388
Sample, Ashley; Zhao, Baozhong; Qiang, Lei et al. (2017) Adaptor protein p62 promotes skin tumor growth and metastasis and is induced by UVA radiation. J Biol Chem 292:14786-14795
Qiang, Lei; Sample, Ashley; Shea, Christopher R et al. (2017) Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis. Autophagy 13:2086-2103
Sample, Ashley; He, Yu-Ying (2017) Autophagy in UV Damage Response. Photochem Photobiol 93:943-955
Qiang, Lei; Sample, Ashley; Liu, Han et al. (2017) Epidermal SIRT1 regulates inflammation, cell migration, and wound healing. Sci Rep 7:14110

Showing the most recent 10 out of 14 publications