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Green Tea Catechins for Prostate Cancer Prevention: Present Achievements and Future Challenges

机译:绿茶儿茶素预防前列腺癌:目前的成就和未来的挑战

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Green tea catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human prostate cancer (PCa) chemoprevention. In the last decades, many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs’ anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets, including cell surface receptors, lipid rafts, and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, and interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentrations that cannot be achieved in vivo. Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs’ bioavailability through still poorly understood mechanisms. Recent efforts to develop delivery systems that increase GTCs’ overall bioavailability, by means of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.
机译:绿茶儿茶素(GTC)是一类化学相关的化合物,通常被归类为抗氧化剂分子。在干预研究的支持下,流行病学证据突显了GTC在人类前列腺癌(PCa)化学预防中的作用远超前途。在过去的几十年中,人们做出了许多努力来获得对GTC行动机制的新见解。现在很明显,GTC的抗癌作用不再单纯地局限于其直接的抗氧化剂/促氧化剂特性。对这一领域知识发展的最新贡献表明,GTC与细胞靶标特异性相互作用,包括细胞表面受体,脂质筏和内质网,通过直接影响转录因子或间接表观遗传机制来调节基因表达,并干扰细胞内各种程度的蛋白水解。在体外观察到的许多影响是剂量和细胞情况的依赖,并且以体内无法达到的浓度发生。肠道吸收不良以及广泛的全身和肠道代谢会通过尚不清楚的机制来影响GTC的生物利用度。最近通过开发生物高分子纳米颗粒来开发可提高GTC总体生物利用度的递送系统的努力,是在PCa化学预防的真实临床场景中转化临床前结果的主要方法。

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