Sunlight-induced skin cancer is the most prevalent cancer in the United States, and UVB is primarily responsible for these cancers. Our studies indicated that oral administration of caffeine or voluntary running wheel exercise (a) decreases tissue fat, (b) inhibits UVB-induced skin carcinogenesis, and (c) enhances apoptosis in UVB-treated epidermis and in skin tumors in SKH-1 mice. We also found that partial lipectomy enhances UVB-induced apoptosis in the epidermis. Our preliminary studies suggest that oral administration of caffeine when combined with voluntary exercise may have a synergistic effect in decreasing tissue fat and stimulating UVB-induced apoptosis. We plan to pursue the following specific aims: 1. Determine the possible molecular mechanisms of voluntary running wheel exercise in combination with orally administered caffeine for 2 weeks on UVB-induced modulation of the p53-independent, ATR/Chk1/cyclin B1-mediated pathway that leads to lethal mitosis (apoptosis) in the epidermis of SKH-1 mice. 2. Determine the effects of removal of the parametrial fat pad (partial lipectomy) on UVB-induced apoptosis and modulation of the p53-independent, ATR/Chk1/cyclin B1-mediated pathway that leads to lethal mitosis (apoptosis) in the epidermis of SKH-1 mice. Effects of exercise in combination with caffeine on UVB-induced apoptosis in the epidermis of partially lipectomized SKH-1 mice will also be studied. 3. Determine the possible synergistic inhibitory effect of exercise in combination with caffeine on UVB-induced skin carcinogenesis in SKH-1 mice. Determine the possible molecular mechanisms of these treatments as well as partial lipectomy on the ATR/Chk1/cyclin B1-mediated pathway that leads to lethal mitosis (apoptosis) in tumors and in areas of the epidermis away from tumors. Possible cytokines that are associated with enhanced skin carcinogenesis will be studied.

Public Health Relevance

Public Health Relevance

TO PUBLIC HEALTH Since physical exercise and/or caffeine intake are conducted by very large segments of the population, research on possible synergy and mechanisms of the potential anticancer effects of exercise, caffeine ingestion and/or fat removal may have broad human significance for cancer prevention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA128997-05
Application #
8305172
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Seifried, Harold E
Project Start
2008-09-18
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$240,319
Indirect Cost
$84,618
Name
Rutgers University
Department
Biology
Type
Schools of Pharmacy
DUNS #
001912864
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Bernard, Jamie J; Lou, You-Rong; Peng, Qing-Yun et al. (2014) Inverse relationship between p53 and phospho-Chk1 (Ser317) protein expression in UVB-induced skin tumors in SKH-1 mice. Exp Mol Pathol 96:126-31
Bernard, Jamie J; Lou, You-Rong; Peng, Qing-Yun et al. (2014) PDE2 is a novel target for attenuating tumor formation in a mouse model of UVB-induced skin carcinogenesis. PLoS One 9:e109862
Bernard, Jamie J; Lou, You-Rong; Peng, Qing-Yun et al. (2014) Parametrial fat tissue from high fat diet-treated SKH-1 mice stimulates transformation of mouse epidermal JB6 cells. J Carcinog Mutagen 5:2157-2518
Conney, Allan H; Lou, You-Rong; Nghiem, Paul et al. (2013) Inhibition of UVB-induced nonmelanoma skin cancer: a path from tea to caffeine to exercise to decreased tissue fat. Top Curr Chem 329:61-72
Lou, Yourong; Peng, Qingyun; Li, Tao et al. (2013) Oral caffeine during voluntary exercise markedly inhibits skin carcinogenesis and decreases inflammatory cytokines in UVB-treated mice. Nutr Cancer 65:1002-13
Lu, Yao-Ping; Lou, You-Rong; Bernard, Jamie J et al. (2012) Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet. Proc Natl Acad Sci U S A 109:9065-70
Lou, You-Rong; Peng, Qing-Yun; Li, Tao et al. (2011) Effects of high-fat diets rich in either omega-3 or omega-6 fatty acids on UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis 32:1078-84
Lu, Yao-Ping; Lou, You-Rong; Peng, Qing-Yun et al. (2011) Caffeine decreases phospho-Chk1 (Ser317) and increases mitotic cells with cyclin B1 and caspase 3 in tumors from UVB-treated mice. Cancer Prev Res (Phila) 4:1118-25
Lou, Yourong; Peng, Qingyun; Nolan, Bonnie et al. (2010) Oral administration of caffeine during voluntary exercise markedly decreases tissue fat and stimulates apoptosis and cyclin B1 in UVB-treated skin of hairless p53-knockout mice. Carcinogenesis 31:671-8