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类黄酮与 PI3K/Akt/mTOR 信号级联:抗肿瘤治疗中的一种潜在相互作用。

Flavonoids and PI3K/Akt/mTOR Signaling Cascade: A Potential Crosstalk in Anticancer Treatment.

机构信息

Department of Biochemistry, J N Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, India.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

出版信息

Curr Med Chem. 2021;28(39):8083-8097. doi: 10.2174/0929867328666210804091548.

Abstract

Cancer is one of the leading causes of death worldwide. A slight decline in mortality has been noted, but the currently available treatment options did not give an expected outcome and are associated with several side effects resulting a substantial economic burden. The advent of plant-based treatment is rising because of its ease of use, ready availability, cost-effectiveness, and low/no toxicity. In recent years, flavonoids with their diverse physico-biological properties have gained the scientific community's attention for the treatment of various forms of cancer. Different flavonoids, especially, flavonols (quercetin, kaempferol, fisetin, and isorhamnetin), flavanones (hesperidin and naringin), and anthocyanins, have shown potent anticancer activities affecting various signaling cascades. Among those, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway is widely known to play a significant role in different physio-cellular activities, which triggers malignant transformation and is considered a key target for anticancer compounds. This pathway plays a vital role in regulating the cell cycle, metabolism, survival, and proliferation. The flavonoids exhibit their anticancer activity via different molecular pathways, including PI3K/Akt/mTOR. In the current piece of paper, our focus is to underpin the action of the above-mentioned flavonoids against different cancers, mainly covering in-vitro data, through PI3K/Akt/mTOR targeting.

摘要

癌症是全球主要死因之一。尽管死亡率略有下降,但目前可用的治疗选择并未产生预期效果,且与多种副作用相关,导致了巨大的经济负担。由于植物性治疗方法具有使用方便、易于获取、成本效益高、毒性低或无毒等特点,其应用日益增多。近年来,具有多种理化特性的黄酮类化合物因其治疗各种癌症的潜力而引起了科学界的关注。不同的黄酮类化合物,特别是黄酮醇(槲皮素、山奈酚、非瑟酮和异鼠李素)、黄烷酮(橙皮苷和柚皮苷)和花青素,已显示出强大的抗癌活性,影响各种信号级联。其中,磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路被广泛认为在不同的生理细胞活动中发挥重要作用,它引发恶性转化,被认为是抗癌化合物的关键靶点。该通路在调节细胞周期、代谢、存活和增殖方面发挥着重要作用。黄酮类化合物通过不同的分子途径发挥抗癌作用,包括 PI3K/Akt/mTOR。在目前的研究中,我们重点关注上述黄酮类化合物通过靶向 PI3K/Akt/mTOR 对不同癌症的作用,主要涵盖体外数据。

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