Phytomelatonin and Cancer Prevention

描述(申请人提供)：本研究的长期目标 该项目是为了更好地了解松果体中提取的褪黑素的作用 腺体，与饮食中摄取的植物褪黑素一起，在 从生物学的角度预防人类恶性肿瘤的生长 时机到了。褪黑素对大鼠肝癌7288CTC的抑制作用 体内生长是通过抑制G蛋白偶联褪黑素实现的 受体介导的cAMP抑制及其对肿瘤的阻断作用 摄取亚油酸(LA)和13-羟基十八碳二烯酸(13-HODE)。这 通过抑制脂肪酸运输蛋白(FATP)功能而发生。13-HODE， 它放大了表皮生长因子EGF-有丝分裂信号通路，是 负责依赖LA的肿瘤生长的有丝分裂信号。假说 要测试的是：来自松果体和饮食来源的褪黑素， 在预防人类肿瘤的发生和发展方面发挥着重要作用 生长；其作用机制是通过褪黑素受体介导的抑制 CAMP依赖的FATP功能和/或表达导致阻断 昼夜节律背景下肿瘤对13-HODE的摄取和产生 结构。第一个目标是评估饮食中褪黑激素对 组织分离的人肿瘤生长和体内LA代谢。第二个目标是 为了进一步确定褪黑激素信号转导机制， 组织分离肿瘤体内LA代谢和生长的调节。第三 目的是研究FATP功能、褪黑素抑制之间的相互作用 信号转导和EGF刺激信号在组织隔离控制中的作用 肿瘤LA的代谢和生长。第四个目标是进一步定义 游离组织中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。建议数 研究将有助于为新的发展提供科学的理论基础 考虑LA摄入量、昼夜节律褪黑激素的饮食建议 补充剂和/或光周期改变以预防和 治疗癌症生长和恶病质。

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.