Bitter melon and chemoprevention of prostate cancer

描述(由申请人提供)：尽管抗癌疗法的发展取得了实质性进展，但癌症的发病率在全球范围内正在增加。控制癌症的一种方法可能是通过饮食预防癌症，饮食可以抑制一个或多个肿瘤事件，降低癌症风险。几个世纪以来，阿育吠陀一直推荐使用苦瓜(苦瓜)作为预防和治疗糖尿病及相关并发症的功能食品。值得一提的是，苦瓜提取物对动物和人类都没有重大副作用。我们最近发现苦瓜提取物在包括前列腺在内的许多癌细胞株中具有抗增殖作用，而不影响正常细胞的生长。苦瓜提取物对前列腺癌细胞bax表达的影响及对PARP的裂解作用。根据我们的初步结果，我们推测苦瓜提取物可能具有抗癌的化学预防作用。为了验证我们的假设，我们将使用前列腺癌作为临床前模型。目的1将通过动物模型评价BME对前列腺癌的化学预防作用，目的2将确定苦瓜提取物抑制人前列腺癌的分子靶点。我们建议的研究结果将阐明苦瓜提取物预防或延缓前列腺癌的概念验证，并将具有很高的翻译研究潜力。本研究结果也将为苦瓜有效成分(S)抗前列腺癌作用的进一步研究奠定基础。 公共卫生相关性：前列腺癌是男性癌症死亡的第二大原因。我们提出的研究将确定苦瓜作为饮食产品在实验性动物模型中预防前列腺癌的作用，最终将转化为临床试验。

DESCRIPTION (provided by applicant): The incidence of cancer is increasing worldwide, in spite of substantial progress in the development of anticancer therapies. One approach to control cancer could be its prevention by diet, which inhibit one or more neoplastic events and reduce the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat diabetes and associated complications. It is noteworthy to mention that bitter melon extract has no major side effects in animals as well as in humans. We have recently discovered an anti-proliferative effect of bitter melon extract in a number of cancer cell lines including prostate without affecting the normal cell growth. Treatment of prostate cancer cells with bitter melon extract modulated Bax expression and induced PARP cleavage. Based on our preliminary results, we hypothesize that bitter melon extract may have chemopreventive activity against cancer. To test our hypothesis, we will use prostate cancer as a preclinical model. Aim 1 will evaluate chemopreventive potential of BME against prostate cancer using animal models, and Aim 2 will determine the molecular targets of bitter melon extract for inhibition of human prostate cancer. The results from our proposed study will elucidate the proof-of-concept for prevention or delay of prostate cancer using bitter melon extract, and will have a high potential for translational research. The results from our study will also provide a foundation for future studies for identification of active bitter melon constituent(s) inhibiting prostate cancer. PUBLIC HEALTH RELEVANCE: Prostate cancer is the second leading cause of cancer death in men. Our proposed study will establish the role of bitter melon as a dietary product for prostate cancer prevention in experimental animal models, which will eventually be translated into clinical trial.