Phytomelatonin and Cancer Prevention

植物褪黑素和癌症预防

• 批准号: 6633246
• 负责人: DAVID BLASK
• 金额: $ 27.99万
• 依托单位: MARY IMOGENE BASSETT HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633246
• 关键词: athymic mouse; breast neoplasms; carcinogenesis inhibitor; circadian rhythms; combination chemotherapy; cyclic AMP; epidermal growth factor; fatty acid binding protein; fatty acid metabolism; forskolin; hepatocellular carcinoma; hormone receptor; hormone regulation /control mechanism; hormone therapy; laboratory rat; linoleate; melatonin; mitogen activated protein kinase; neoplasm /cancer chemotherapy; neoplasm /cancer nutrition therapy; nonhuman therapy evaluation; nutrition aspect of cancer; nutrition related tag; plant extracts; protein kinase A

DESCRIPTION (provided by applicant): The long-term goal of this research project is to better understand the role of melatonin derived from the pineal gland, in conjunction with phytomelatonin ingested in the diet, in the prevention of the growth of human malignancies in the context of biological timing. Melatonin inhibition of tissue-isolated tumor (rat hepatoma 7288CTC) growth in vivo occurs via inhibitory G protein-coupled melatonin receptor-mediated suppression of cAMP and a resultant blockade of tumor linoleic acid (LA) uptake and 13-hydroxyoctadecadienoic acid (13-HODE). This occurs via inhibition of fatty acid transport protein (FATP) function. 13-HODE, which amplifies the epidermal growth factor EGF-mitogenic signaling pathway, is the mitogenic signal responsible for LA-dependent tumor growth. The hypothesis to be tested is: Melatonin, derived from the pineal gland and dietary sources, plays a significant role in the prevention of human tumor development and growth; the mechanism of action is via melatonin receptor-mediated suppression of cAMP-dependent FATP function and/or expression leading to a blockade of tumor LA uptake and production of 13-HODE in the context of circadian time structure. The first aim is to assess the effects of dietary melatonin on tissue-isolated human tumor growth and LA metabolism in vivo. The second aim is to further define the melatonin signal transduction mechanisms involved in the regulation of tissue-isolated tumor LA metabolism and growth in vivo. The third aim is to examine the interactions among FATP function, melatonin inhibitory signaling, and EGF stimulatory signaling in the control of tissue-isolated tumor LA metabolism and growth. The fourth aim is to further define the circadian rhythm regulation of FA metabolism simultaneously in tissue-isolated tumors and contralateral fat pads and the role of melatonin. The proposed studies will help to provide a scientific rationale for the development of new dietary recommendations that consider LA intake, circadian-timed melatonin supplementation and/or photoperiodic alterations for the prevention and treatment of cancer growth and cachexia.

描述（由申请人提供）：本研究的长期目标 该项目是为了更好地了解来自松果体的褪黑激素的作用 腺体，与饮食中摄入的植物褪黑素结合，在 从生物角度预防人类恶性肿瘤的生长 定时。褪黑素抑制组织分离肿瘤（大鼠肝癌7288CTC） 体内生长通过抑制性 G 蛋白偶联褪黑激素发生 受体介导的 cAMP 抑制以及由此产生的肿瘤阻断 亚油酸 (LA) 摄取和 13-羟基十八二烯酸 (13-HODE)。这 通过抑制脂肪酸转运蛋白 (FATP) 功能而发生。 13-霍德， 它放大表皮生长因子EGF促有丝分裂信号通路，是 负责 LA 依赖性肿瘤生长的有丝分裂信号。假设 要测试的是： 褪黑激素，源自松果体和饮食来源， 对预防人类肿瘤的发展具有重要作用 生长;作用机制是通过褪黑激素受体介导的抑制 cAMP 依赖性 FATP 功能和/或表达的影响导致阻断 昼夜节律背景下肿瘤 LA 的摄取和 13-HODE 的产生 结构。第一个目的是评估膳食褪黑激素对 组织分离的人类肿瘤生长和体内 LA 代谢。第二个目标是 进一步明确褪黑激素信号转导机制 体内组织分离肿瘤 LA 代谢和生长的调节。第三个 目的是检查 FATP 功能、褪黑激素抑制之间的相互作用 信号传导和 EGF 刺激信号传导控制组织隔离 肿瘤LA代谢和生长。第四个目标是进一步明确 在组织隔离中同时调节 FA 代谢的昼夜节律 肿瘤和对侧脂肪垫与褪黑素的作用。拟议的 研究将有助于为新产品的开发提供科学依据 考虑洛杉矶摄入量、昼夜节律褪黑激素的饮食建议 补充和/或光周期改变以预防和 治疗癌症生长和恶病质。