Prostate cancer and inositol hexaphosphate: efficacy and mechanisms.
Prostate cancer and inositol hexaphosphate: efficacy and mechanisms.
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发表时间：
2005-07
影响因子：
2
通讯作者：
R. Singh;R. Agarwal
中科院分区：
文献类型：
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作者：
R. Singh;R. Agarwal
现在有大量的科学数据表明膳食和非膳食植物化学物质在预防和控制前列腺癌 (PCA) 生长和进展方面的潜在作用。 PCA 是一种老年男性疾病，与大多数其他癌症相比，其生长和进展速度相对较慢，因此是预防性干预的候选疾病。总体而言，PCA 的生长和进展涉及异常的有丝分裂和生存信号传导以及细胞周期进展失调，并伴随着多年来遗传和表观遗传变化的逐渐积累。 PCA 的生长和进展涉及多种机制，包括生长、存活和血管生成因子及其受体的过度表达，以及肿瘤抑制因子 p53、视网膜母细胞瘤和细胞周期蛋白依赖性激酶抑制剂的丢失/减少。因此，针对这些分子事件的植物化学物质可能在 PCA 预防和/或治疗中发挥有前景的作用。六磷酸肌醇 (IP6) 是大多数谷物、豆类、坚果、油籽和大豆的主要成分。作为非处方膳食/营养补充剂口服，被认为具有多种健康益处，且没有任何已知的毒性。已在许多人类、小鼠和大鼠前列腺癌细胞中观察到 IP6 的体外抗癌功效。已完成的研究还表明，口服IP6可抑制裸鼠体内人PCA异种移植物的生长，且无毒性。在最近完成的一项试点研究中，我们在 TRAMP 模型中观察到 IP6 对前列腺肿瘤发生具有类似的预防作用。机制研究表明，IP6 的靶标是 PCA 细胞中的有丝分裂和生存信号传导以及细胞周期进程。 IP6 还被证明可以靶向与血管生成相关的分子事件。此外，IP6 具有针对 PCA 的整体功效的多效性分子靶标，因此可能是预防干预人类这种恶性肿瘤的合适候选药物。
There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.