Inhibitory effects of caffeine, exercise and lipectomy on UVB-induced skin cancer

咖啡因、运动和脂肪切除术对 UVB 诱发的皮肤癌的抑制作用

• 批准号: 7688537
• 负责人: Yaoping Lu
• 金额: $ 24.78万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7688537
• 关键词: Adipocytes; Animals; Apoptosis; Apoptotic; Area; Caffeine; Dermal; Diet; Epidermis; Excision; Exercise; Fatty acid glycerol esters; Human; Inflammatory; Ingestion; Intake; Lipectomy; Malignant Neoplasms; Mediating; Mitosis; Molecular; Mus; Oral Administration; Parametrial; Pathway interactions; Play; Population Research; Public Health; Reporting; Role; Running; Skin Cancer; Skin Carcinogenesis; Skin Neoplasms; TP53 gene; Testing; Thick; Tissues; UV induced; UVB induced; Ultraviolet B Radiation; United States; cancer prevention; cyclin B1; cytokine; premature; public health relevance; sunlight-induced; tumor

DESCRIPTION (provided by applicant): 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: 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.

描述（由申请人提供）： 阳光引起的皮肤癌是美国最普遍的癌症，UVB主要负责这些癌症。我们的研究表明，口服咖啡因或自愿运动轮运动（a）减少组织脂肪，（b）抑制UVB诱导的皮肤致癌作用，（c）增强了UVB治疗的表皮和SKH-1小鼠的皮肤肿瘤的凋亡。我们还发现，部分脂肪切除术增强了UVB诱导的表皮凋亡。我们的初步研究表明，与自愿运动结合使用咖啡因时，对减少组织脂肪和刺激UVB诱导的细胞凋亡可能具有协同作用。我们计划追求以下具体目标：1。在UVB诱导的p53非依赖性，ATR/CHK1/Cyclin B1介导的途径中，确定自愿跑步轮运动的可能分子机制，并结合口服的caffeine 2周，从而导致致命的有效症状（Apoptosis）。 2。确定去除参数脂肪垫（部分脂肪切除术）对UVB诱导的凋亡的影响，并调节p53独立，ATR/CHK1/Cyclin B1介导的途径，该途径导致SKH-1 MICE表皮中的致死有丝见有丝核（凋亡）。还将研究运动对部分脂肪切除的SKH-1小鼠表皮中UVB诱导的凋亡的影响。 3。确定运动与咖啡因结合使用咖啡因对SKH-1小鼠中UVB诱导的皮肤致癌作用的可能协同抑制作用。确定这些治疗方法的可能分子机制以及对ATR/CHK1/Cyclin B1介导的途径的部分脂肪切除术，该途径导致肿瘤和表皮区域的致死有丝分裂（凋亡）。将研究与皮肤癌变相关的可能的细胞因子。公共卫生相关性：与公共卫生相关性，因为体育锻炼和/或咖啡因的摄入量是由大量人群进行的，研究可能的协同作用和机制的研究，对运动的潜在抗癌作用，摄入咖啡因摄入和/或脂肪去除可能具有广泛的人类预防癌症意义。