Title:Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Volume: 24
Issue: 13
关键词:
五环三萜类化合物，半合成衍生物，抗肿瘤剂，作用机制，信号通路，分子靶标。
摘要: 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.
