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Kava extract, Flavokawains and Bladder Cancer Prevention

卡瓦提取物、黄酮川苷与膀胱癌预防

基本信息

批准号：
6920812
负责人：
Xiaolin Zi
金额：
$ 10.29万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-13 至 2007-06-30
项目状态：
已结题

项目摘要

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。卡瓦在南太平洋群岛作为饮料、药物和社会宗教功能有着悠久的历史，类似于西方对葡萄酒的使用。几个世纪以来，饮用传统卡瓦水制剂而没有产生重大副作用，这与斐济、瓦图和西萨摩亚等饮用卡瓦国家的癌症发病率较低且不寻常的性别比（女性癌症发病率高于男性）相关。我们最近发现卡瓦提取物和提取物中的三种查尔酮可以作为膀胱癌细胞凋亡的诱导剂。此外，我们发现黄酮卡因A（一种主要的查耳酮）的凋亡作用与诱导线粒体凋亡途径和抑制NF-κB介导的抗凋亡途径有关。由于研究表明，导致细胞凋亡抵抗的细胞凋亡途径的频繁改变可能是膀胱癌发生所必需的，因此可以诱导细胞凋亡和抑制抗细胞凋亡信号传导的药物值得在膀胱癌预防中进行研究。我们假设含有黄卡因 A 的卡瓦提取物通过强烈诱导癌前细胞和恶性细胞凋亡而具有抗肿瘤和化学预防膀胱癌的活性。我们的具体目标有两个。首先，我们将确定卡瓦提取物和黄花素A减少裸鼠移植膀胱癌细胞肿瘤形成和生长的能力，以及卡瓦提取物发挥作用所需的黄素卡因A。其次，我们将定义并比较黄素卡瓦素 A 和卡瓦提取物对正常、癌前和恶性膀胱癌细胞中凋亡和抗凋亡信号传导的作用机制。从这些研究中获得的知识应该使我们能够 1) 设计出更好的卡瓦产品，其中优化了黄酮卡瓦因 A 和卡瓦内酯的比例，用于膀胱癌预防的转化研究； 2) 设计更好的流行病学研究，以调查卡瓦产品或卡瓦的使用与膀胱癌风险（特别是膀胱癌风险）和总体健康影响之间的关系。