Allium Compounds in Control of Human Prostate Cancer

描述：(由申请人提供)这项探索性拨款旨在为大蒜中的蒜衍生物在控制人类健康方面建立一个新的作用。 前列腺癌通过起到抗雄激素的作用。我们的初步观察显示 当雄激素反应性人前列腺癌细胞(LNCaP)孵育时 在体外，蒜衍生物发生了两个事件：(A)增殖 LNCaP细胞率明显降低；(B)睾酮浓度 在细胞生长的介质中以及在 在细胞本身。此外，当睾丸激素被重新添加到 预先暴露于蒜衍生物的LNCaP细胞的培养液中， 细胞增殖的初始速度仅部分恢复。这些 初步结果有力地表明，大蒜诱导的细胞抑制 睾丸激素的增殖和加速排出是有联系的。我们 假设大蒜衍生物通过以下方式增加睾酮消失 加速转化为不活跃的代谢物，从而减弱这种作用 睾丸激素对前列腺的影响。为了检验这一假设的真实性，我们 应测量睾酮到双氢睾酮(DHT)的转化率， 更强的代谢物，通过5-阿尔法还原酶，以及 一系列无活性的睾酮代谢物，用气相色谱-质谱法测定。 在这些实验的同时，我们将确定 蒜衍生物对人前列腺癌细胞生长的抑制作用 无论是通过细胞凋亡还是细胞停滞。我们将确定细胞周期中的什么位置 发生生长抑制，无论是否诱导细胞凋亡，以及是否 在后来的实验中，特定信号转导蛋白OCC的变化，我们 最有可能研究蒜衍生物对调节蛋白的影响 与修改细胞周期转录的这些条件相关 (即细胞周期蛋白B，cdk 2)。这些研究将在第二年延长。 检测蒜衍生物对人前列腺癌LNCaP细胞的影响 C4-2)，表现出雄激素受体，但对其营养缺乏反应 效果。LNCaP和LNCaP C4-2细胞株共同作用于 分别适用于早期前列腺癌的模型 雄激素敏感型前列腺癌和后来的前列腺癌 雄激素操作。这些研究应该提供一种创造性的方法来 预防和控制前列腺癌可行且COSI有效， 并应导致在关联某些饮食方面的创新进展 修饰和前列腺癌。

DESCRIPTION: (provided by the applicant) This exploratory grant seeks to establish a novel role for allium derivatives from garlic in control of human prosta cancer by acting as anti-androgens. Our preliminary observations reveal that when androgen-responsive human prostate cancer cells (LNCaP) are incubated with allium derivatives in vitro, two events take place: (a) the proliferation rate of the LNCaP cells is markedly reduced and (b) testosterone concentration rapidly decreases in both the media in which the cells are growing as well as in the cells themselves. Furthermore, when testosterone is added back to the media of LNCaP cells previously exposed to allium derivatives, the decrease in initial rate of cell proliferation is only partially restored. These preliminary results strongly suggest that allium-induced inhibition of cell proliferation and accelerated removal of testosterone are linked. We hypothesize that allium derivatives increase testosterone disappearance by accelerating conversion to inactive metabolites thereby diminishing the action of testosterone on the prostate. To test I validity of this hypothesis, we shall measure the conversion rate of testosterone to dihydrotestosterone (DHT), a more potent metabolite, through 5-alpha reductase, and the formation rate of a series of inactive testosterone metabolites, a determined by GC-MS methods. Concurrent with these experiments, we shall determine the mechanism of inhibition of growth of human prostat cancer cells by allium derivatives, whether by apoptosis or cytostasis. We shall determine where in the cell cycle growth inhibition occurs, whether or not apoptosis is induced, and whether changes in specific signal transduction proteins occ in later experiments, we shall examine effects of allium derivatives on regulatory proteins most likely to be relevant unc these conditions in modifying cell cycle transcription (i.e., cyclin B, cdk 2). These studies will then be extended in the second year to examine effects of allium derivatives on human prostate cancer cells (LNCaP C4-2) that exhibit androgen receptors but are non-responsive to its trophic effects. Together, the LNCaP and LNCaP C4-2 cell lines should serve as appropriate models, respectively, for early prostate cancer that is androgen-sensitive and later prostate cancer that is largely unresponsive to androgen manipulations. These studies should provide a creative approach to prevention and control of prostate cancer that is feasible and cosi effective, and should lead to an innovative advance in correlating certain dietary modifications and prostate cancer.