Bcl-2 proteins-targets for chemoprevention /Chemotherapy

描述(由申请人提供)： 这一建议的基本原理在很大程度上是基于我们最近令人兴奋的研究，这些研究表明，选定的多酚，包括红茶和绿茶的提取物，可能通过靶向Bcl-2家族的蛋白质而诱导细胞凋亡(程序性细胞死亡)。在大约70%的前列腺癌和乳腺癌中，bcl2和bclx L过表达，从而阻止了癌细胞在放疗和化疗的情况下死亡。因此，我们有理由推测，在体外能够中和Bcl2家族蛋白保护作用的饮食化合物在体内可能具有化学预防活性。在此前提下，我们建议使用生物物理方法筛选天然饮食化合物的大型文库，以抑制Bcl一x、L和Bcl一2蛋白的表达，并研究这类化合物对人癌细胞的细胞毒作用。我们预计，我们的研究将产生有希望的促细胞凋亡化合物，这些饮食物质不仅将在癌症化学预防方面产生影响，还将在癌症治疗的新临床疗法的开发中产生影响。

DESCRIPTION (provided by applicant): The rationale for this proposal is based, in large measure, upon our recent exciting studies that show that selected polyphenols, including extracts from black and green tea, may be inducing apoptosis (programmed cell-death) by targeting proteins of the Bcl-2 family. Bcl-2 and Bcl-x L are over-expressed in approximately 70% of prostate and breast cancers, preventing cancer cells from dying despite radiation and chemotherapy. As such, it is reasonable to hypothesize that dietary compounds capable to neutralize the protective effects of Bcl-2 family proteins in vitro may possess chemopreventive activity in vivo. On the premises, we propose to use biophysical assays to screen large libraries of natural dietary compounds for inhibition of Bcl-x L and Bcl-2 proteins and to study the cytotoxic effects of such compounds on human cancer cell lines. We anticipate that promising pro-apoptotic compounds would arise from our studies and that such dietary substances would have an impact not only in cancer chemoprevention but also in the development of new clinical therapies for the treatment of cancer.