Markov Andrey V, Zenkova Marina A, Logashenko Evgeniya B
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, Novosibirsk. Russian Federation.
Siberian Branch Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, 630090, Novosibirsk. Russian Federation.
Curr Med Chem. 2017;24(13):1277-1320. doi: 10.2174/0929867324666170112115313.
Pentacyclic triterpenoids are a large class of natural isoprenoids that are widely biosynthesized in higher plants. These compounds are potent anticancer agents that exhibit antiproliferative, antiangiogenic, antiinflammatory and proapoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not yet been established. To date, a huge number of semisynthetic derivatives have been synthesized in different laboratories on the basis of triterpenoid scaffolds, and many have been assayed for their biological activities. The present review focuses on natural triterpenoids of the oleanane-, ursane- and lupane-types and their semisynthetic derivatives. Here, we summarize the diverse cellular and molecular targets of these compounds and the signal pathways involved in the performance of their antitumour actions. Among the most relevant mechanisms involved are cell cycle arrest, apoptosis and autophagy triggered by the effect of triterpenoids on TGF-β and HER cell surface receptors and the downstream PI3KAkt- mTOR and IKK/NF-kB signaling axis, STAT3 pathway and MAPK cascades.
五环三萜类化合物是一大类天然异戊二烯类化合物，在高等植物中广泛生物合成。这些化合物是有效的抗癌剂，具有抗增殖、抗血管生成、抗炎和促凋亡活性。尽管已经报道了它们对多种途径的影响，但尚未建立统一的作用机制。迄今为止，不同实验室已基于三萜骨架合成了大量半合成衍生物，并对许多衍生物的生物活性进行了测定。本综述重点关注齐墩果烷型、乌苏烷型和羽扇豆烷型天然三萜类化合物及其半合成衍生物。在此，我们总结了这些化合物多样的细胞和分子靶点以及其抗肿瘤作用所涉及的信号通路。其中最相关的机制包括三萜类化合物对TGF-β和HER细胞表面受体以及下游PI3KAkt-mTOR和IKK/NF-kB信号轴、STAT3途径和MAPK级联反应的影响所触发的细胞周期阻滞、凋亡和自噬。
