Bitter melon and chemoprevention of prostate cancer

描述（由申请人提供）：尽管抗癌疗法的开发取得了实质性进展，但癌症的发病率在全球范围内仍在增加。控制癌症的一种方法可能是通过饮食进行预防，从而抑制一种或多种肿瘤事件并降低癌症风险。几个世纪以来，阿育吠陀一直推荐使用苦瓜（Momorea charantia）作为预防和治疗糖尿病及相关并发症的功能性食物。值得一提的是，苦瓜提取物在动物和人类中没有重大副作用。我们最近发现苦瓜提取物在许多癌细胞系中具有抗增殖作用，包括前列腺，而不影响正常细胞生长。用苦瓜提取物处理前列腺癌细胞调节Bax表达并诱导PARP裂解。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活性。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。目的一是利用动物模型评价苦瓜提取物对前列腺癌的化学预防作用，目的二是确定苦瓜提取物抑制前列腺癌的分子靶点。我们提出的研究结果将阐明使用苦瓜提取物预防或延迟前列腺癌的概念验证，并将具有很高的转化研究潜力。我们的研究结果也将为未来鉴定苦瓜活性成分抑制前列腺癌的研究提供基础。 公共卫生相关性：前列腺癌是男性癌症死亡的第二大原因。我们提出的研究将在实验动物模型中建立苦瓜作为预防前列腺癌的饮食产品的作用，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.