Inhibition of Prostate Carcinogenesis by Apigenin

芹菜素抑制前列腺癌发生

基本信息

批准号：
6576464
负责人：
SANJAY GUPTA
金额：
$ 7.65万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2004-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer is the most common and one of the leading causes of cancer-related deaths in American males. To reduce the incidence of this disease, chemoprevention through dietary intervention appears to be an encouraging approach. Epidemiological studies suggest that high consumption of fruits and vegetables may be associated with a reduced risk of prostate cancer. These studies are consistent with the observations that Asian men who consume low fat, high-fiber diet rich in flavonoids have lowest prostate cancer incidence in the world. Laboratory studies in cell culture systems have demonstrated that apigenin, a common flavonoid present in fruits and vegetables afford protection against many types of epithelial cancers including skin, colon, and breast. Consistent with this notion, our recent studies (BBRC 287:914-20, 2001 & Oncogene, In Press) are noteworthy where we have shown i) selective response of apigenin against normal versus prostate carcinoma cells, ii) inhibition of cell growth, iii) induction of apoptosis in a wide range of human prostate carcinoma cells. An important implication of these findings could be that apigenin may have preventive effects against the development of prostate cancer in humans. This could be an effective prevention by delay. If this occurs then apigenin can slow the process of cancer cell growth in humans, it will be important for the survival and quality of life of patients diagnosed with prostate cancer at an early stage. However, these associations remain inconclusive because there is no such study conducted so far which could provide evidence-based prevention and intervention of apigenin on prostate carcinogenesis. In the present application, we will test this hypothesis in a recently developed transgenic animal model TRAMP (transgenic adenocarcinoma mouse prostate) that mimics progressive forms of human prostatic disease. The central hypothesis to be tested in this application is that apigenin will impart cancer-preventive and possibly cancer-therapeutic effect by modulating the apoptotic machinery of prostate cancer cells in TRAMP model of prostate carcinogenesis. Both in vivo tumor growth and apoptosis will be monitored serially during the experimental protocol by our recently perfected technique of MRI and 99M-Tc-labeled annexin V. A successful completion of this application will set a platform to define the role of apigenin as a promising agent against prevention and possibly therapy of prostate cancer in humans.

描述（由申请人提供）：前列腺癌是美国男性最常见的癌症，也是导致癌症相关死亡的主要原因之一。为了降低这种疾病的发病率，通过饮食干预进行化学预防似乎是一种令人鼓舞的方法。流行病学研究表明，大量食用水果和蔬菜可能与降低前列腺癌的风险有关。这些研究与观察结果一致，即食用富含类黄酮的低脂肪、高纤维饮食的亚洲男性前列腺癌发病率是世界上最低的。细胞培养系统的实验室研究表明，芹菜素（一种存在于水果和蔬菜中的常见黄酮类化合物）可以预防多种类型的上皮癌，包括皮肤癌、结肠癌和乳腺癌。与这一观点一致，我们最近的研究（BBRC 287:914-20, 2001 & Oncogene, In Press）值得注意，其中我们显示了 i) 芹菜素对正常细胞与前列腺癌细胞的选择性反应，ii) 细胞生长的抑制，iii ) 诱导多种人类前列腺癌细胞凋亡。这些发现的一个重要意义可能是芹菜素可能对人类前列腺癌的发展具有预防作用。这可能是一种有效的延迟预防方法。如果发生这种情况，那么芹菜素可以减缓人类癌细胞的生长过程，这对于早期诊断出前列腺癌的患者的生存和生活质量非常重要。然而，这些关联仍然没有结论，因为迄今为止还没有进行此类研究可以为芹菜素对前列腺癌发生的预防和干预提供循证证据。在本申请中，我们将在最近开发的转基因动物模型 TRAMP（转基因小鼠前列腺腺癌）中测试这一假设，该模型模拟人类前列腺疾病的进展形式。本申请要测试的中心假设是芹菜素将通过在前列腺癌发生的TRAMP模型中调节前列腺癌细胞的凋亡机制来赋予癌症预防和可能的癌症治疗作用。在实验方案期间，将通过我们最近完善的 MRI 和 99M-Tc 标记的膜联蛋白 V 技术连续监测体内肿瘤生长和细胞凋亡。该应用的成功完成将为定义芹菜素作为有前途的药物的作用奠定一个平台。预防和可能治疗人类前列腺癌的药物。