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 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激素一起， 预防人类恶性肿瘤的生长 时机褪黑素对组织分离肿瘤（大鼠肝癌7288 CTC）的抑制作用 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抑制和肿瘤阻断 亚油酸（LA）摄取和13-羟基十八碳二烯酸（13-HODE）。这 通过抑制脂肪酸转运蛋白（FATP）功能发生。13-HODE， 其放大表皮生长因子EGF促有丝分裂信号通路， 有丝分裂信号负责LA依赖性肿瘤生长。的假设 要测试的是：褪黑激素，来自松果体和饮食来源， 在预防人类肿瘤发展中起重要作用， 生长;作用机制是通过褪黑素受体介导的抑制 cAMP依赖性FATP功能和/或表达的抑制，导致 肿瘤LA摄取和13-HODE的产生与昼夜节律时间的关系 结构第一个目的是评估饮食褪黑激素对 组织分离的人肿瘤生长和体内LA代谢。第二个目标是 为了进一步定义参与的褪黑激素信号传导机制， 体内组织分离肿瘤LA代谢和生长的调节。第三 目的是研究FATP功能、褪黑素抑制 信号和EGF刺激信号在组织分离的控制 肿瘤LA代谢和生长。第四个目标是进一步确定 同时在离体组织中FA代谢的昼夜节律调节 肿瘤和对侧脂肪垫以及褪黑素的作用。拟议 研究将有助于为开发新的 饮食建议，考虑LA摄入量，昼夜定时褪黑激素 补充和/或光周期性改变，以预防和 治疗癌症生长和恶病质。