Kava extract, Flavokawains and Bladder Cancer Prevention

卡瓦提取物、黄酮川苷与膀胱癌预防

• 批准号: 6818032
• 负责人: Xiaolin Zi
• 金额: $ 10.23万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-13 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6818032
• 关键词: alternative medicine; antineoplastics; apoptosis; athymic mouse; beverages; bladder neoplasm; cancer prevention; carcinogenesis; cell transformation; chemoprevention; flavonoids; ketones; medicinal plants; mitochondria; neoplastic cell; neoplastic growth; nonhuman therapy evaluation; nuclear factor kappa beta; plant extracts

DESCRIPTION (provided by applicant) Bladder cancer remains a major public health burden. Kava has a long history of serving as a beverage, medicine and in socio-religious functions in the South Pacific Islands, similar to the Western use of wine. Consumption of traditional aqueous kava preparation without major side effects for centuries correlates with lower and uncustomary sex ratio (more cancer in women than men) of, cancer incidences in kava-drinking countries such as Fiji, Vatu and Western Samoa. We recently have identified a kava extract and three chalcones from the extract as inducers of apoptosis in bladder cancer cells. Furthermore, we found that the apoptotic effect of flavokawain A, a major chalcone, was associated with the induction of the mitochondrial apoptotic pathway and inhibition of NF-kappa B mediated anti-apoptotic pathway. Since studies suggest that frequent alterations in apoptotic pathways leading to resistance of apoptosis may be obligatory for bladder carcinogenesis, agents that can induce apoptotic and inhibit anti-apoptotic signaling deserve study in bladder cancer prevention. We hypothesize that kava extracts that contain flavokawain A have antineoplastic and chemopreventive activities against bladder cancer via a robust induction of apoptosis in pre-malignant and malignant cells. Our specific aims are two fold. First, we will determine the ability of kava extracts and flavokwain A to reduce tumor formation and growth of the transplanted bladder cancer cells in nude mice, and the requirement of flavokawain A for kava extracts' effect. Second, we will define and compare the mechanisms of flavokawain A and kava extracts' actions on apoptotic and anti-apoptotic signaling in normal, pre-malignant and malignant bladder cancer cells. The knowledge generated from these studies should allow us to 1) devise better kava product with optimized ratio of flavokawain A and kavalactones for translation research in bladder cancer prevention; 2) design better epidemiological study to investigate the relationship between use of kava products or kava and risk of bladder cancer in particular and health effects in general.

描述（由申请人提供） 膀胱癌仍然是主要的公共卫生负担。卡瓦（Kava）在南太平洋岛屿上充当饮料，医学和社会宗教功能的悠久历史，类似于西方使用葡萄酒。 几个世纪以来，消费传统的Kava制剂而没有重大副作用，与较低和不稳态的性别比（女性的癌症多于男性），卡瓦饮酒国家的癌症发生率，例如斐济，瓦图和西部萨摩亚。我们最近已经确定了一种Kava提取物和三个来自提取物的墨西哥蛋白酶作为膀胱癌细胞凋亡的诱导剂。此外，我们发现，主要的chalcone A Flavokawain A的凋亡作用与线粒体凋亡途径的诱导和NF-KAPPA B介导的抗源自途径的抑制有关。由于研究表明，导致凋亡抗性的凋亡途径的频繁改变可能是膀胱致癌作用的必要性，因此可以诱导凋亡并抑制抗凋亡信号的药物应在膀胱癌预防中得到研究。我们假设含有黄牛蛋白A的Kava提取物通过强烈的恶性和恶性细胞中凋亡的强烈诱导，具有针对膀胱癌的抗肿瘤和化学预防活性。我们的具体目标是两个折。首先，我们将确定Kava提取物和Flavokwain A减少裸鼠移植的膀胱癌细胞的肿瘤形成和生长的能力，以及对Kava提取物效应的Flavokawain A的需求。其次，我们将定义和比较Flavokawain A和Kava提取对正常，恶性和恶性膀胱癌细胞中凋亡和抗凋亡信号传导的作用。这些研究产生的知识应使我们能够达到1）更好地设计了更好的卡瓦产品，具有优化的黄牛蛋白A和卡瓦乳糖酮的优化比例，用于预防膀胱癌的翻译研究； 2）设计更好的流行病学研究，以调查使用Kava产品或Kava的使用与膀胱癌的风险以及一般健康影响之间的关系。