Deregulation of PI3K/Akt/mTOR Signaling Pathways by Isoflavones and its Implication in Cancer Treatment
Deregulation of PI3K/Akt/mTOR Signaling Pathways by Isoflavones and its Implication in Cancer Treatment
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DOI：
10.2174/18715206113139990117
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发表时间：
2013-09-01
影响因子：
2.8
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Ahmad, Aamir;Biersack, Bernhard;Sarkar, Fazlul H.
癌症仍然是一种难以控制的疾病，因为与其发展和进展相关的许多信号通路的失调。一种这样的途径是磷酸肌醇3-激酶（PI 3 K）-蛋白激酶B（Akt）-哺乳动物雷帕霉素靶（mTOR）信号传导网络，已知其与许多人类癌症的不良预后相关。在体外、体内和临床上对该信号网络的靶向抑制表明这是抑制癌细胞增殖和转移的有效策略。为此，使用天然药物进行治疗干预吸引了新的兴趣，因为它们的无毒作用以及它们调节多种途径的能力。研究表明，这些化合物对PI 3 K/Akt/mTOR途径中的多种因子具有强效抗癌活性。除了用作各种癌症的治疗剂之外，有证据支持马诺酮在增强放射治疗中的作用以及其他常规治疗药物的抗癌作用。在这篇综述文章中，我们讨论了我们目前对PI 3 K/Akt/mTOR信号通路的调节的理解，这可能是负责他们在体外和体内观察到的活性对人类癌症。
Cancer remains a difficult disease to manage because of the deregulation of numerous signaling pathways that are associated with its development and progression. One such pathway is the phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) - mammalian target of rapamycin (mTOR) signaling network, which is known to be associated with poor prognosis in many human cancers. Targeted inhibition of this signaling network in vitro, in vivo and in clinics has suggested this to be an effective strategy for the inhibition of cancer cells' proliferation and metastases. Towards this end, the use of natural agents for therapeutic intervention has attracted renewed interest because of their non-toxic effects as well as their ability to modulate multiple pathways. Investigations involving isoflavones have suggested a potent anticancer activity of these compounds against multiple factors in the PI3K/Akt/mTOR pathway. In addition to their use as therapeutic agents against various cancers, there is evidence to support the role of isoflavones in potentiation of radiation therapy as well as the anticancer action of other conventional therapeutic drugs. In this review article, we discuss our current understanding of the regulation of PI3K/Akt/mTOR signaling pathways by isoflavones, which could be responsible for their observed in vitro and in vivo activity against human cancers.