title: Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives.
abstract: 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.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, Novosibirsk. Russian Federation.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Markov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, Novosibirsk. Russian Federation.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zenkova
authors.affiliation: Siberian Branch Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, 630090, Novosibirsk. Russian Federation.
authors.forename: Evgeniya B
authors.initials: EB
authors.lastname: Logashenko
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D053978:Pentacyclic Triterpenes
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D009828:Oleanolic Acid; D016212:Transforming Growth Factor beta; D014315:Triterpenes; C413246:oleanane; C000606873:ursane; D053978:Pentacyclic Triterpenes; C480546:lupane
keywords: Pentacyclic triterpenoids; antitumour; mechanism of action; molecular targets; semisynthetic derivatives; signaling pathways