Inhibition of mTOR Signaling by Quercetin in Cancer Treatment and Prevention
Inhibition of mTOR Signaling by Quercetin in Cancer Treatment and Prevention
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DOI：
10.2174/18715206113139990114
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发表时间：
2013-09-01
影响因子：
2.8
通讯作者：
Bruening, Ansgar
中科院分区：
文献类型：
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作者：
Bruening, Ansgar
槲皮素是我们日常饮食中丰富的微量营养素。几种有益的健康效应与这种生物素的饮食摄入有关，包括缓解慢性炎症和动脉粥样硬化的作用。各种体外数据表明，槲皮素可能通过与多种癌症相关途径相互作用而用于癌症治疗目的。其中，最近的数据显示槲皮素可以抑制癌细胞中的mTOR活性。已经直接描述了槲皮素对mTOR信号传导途径的抑制，并且可以进一步从其对PI 3 K依赖性Akt刺激、AMP依赖性蛋白激酶活化和错构蛋白上调的干扰中推断。槲皮素干扰mTOR活性和PI 3 K/Akt信号通路活化的能力使槲皮素具有作为双特异性mTOR/PI 3 K抑制剂的优势。mTOR复合物，通常在癌症中过度活化，是稳态的关键调节剂，控制导致细胞生长、蛋白质生物合成和自噬的基本途径。槲皮素通过多种途径抑制mTOR活性的能力使得这种在其他方面安全的生物素成为治疗癌症和与mTOR失调相关的其他疾病的有趣工具。
Quercetin is an abundant micronutrient in our daily diet. Several beneficial health effects are associated with the dietary uptake of this bioflavonoid, including alleviating effects on chronic inflammation and atherosclerosis. A variety of in vitro data indicate a possible use of quercetin for cancer treatment purposes through its interaction with multiple cancer-related pathways. Among these, recent data reveal that quercetin can inhibit mTOR activity in cancer cells. Inhibition of the mTOR signaling pathway by quercetin has directly been described and can further be deduced from its interference with PI3K-dependent Akt stimulation, AMP-dependent protein kinase activation and hamartin upregulation. The ability of quercetin to interfere with both mTOR activity and activation of the PI3K/Akt signaling pathway gives quercetin the advantage to function as a dual-specific mTOR/PI3K inhibitor. The mTOR complex, often hyperactivated in cancer, is a crucial regulator of homeostasis controlling essential pathways leading to cell growth, protein biosynthesis and autophagy. The ability of quercetin to inhibit mTOR activity by multiple pathways makes this otherwise safe bioflavonoid an interesting tool for the treatment of cancers and other diseases associated with mTOR deregulation.