Unifying mechanisms of action of the anticancer activities of triterpenoids and synthetic analogs.

Anti-cancer Agents in Medicinal Chemistry
Stephen SafeIndira Jutooru

Abstract

Triterpenoids such as betulinic acid (BA) and synthetic analogs of oleanolic acid [2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)] and glycyrrhetinic acid [2-cyano-3,11-dioxo-18β-oleana-1,12-dien-30-oc acid (CDODA)] are potent anticancer agents that exhibit antiproliferative, antiangiogenic, anti-inflammatory and pro-apoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not been reported. Studies in this laboratory have now demonstrated that several triterpenoids including BA and some derivatives, celastrol, methyl ursolate, β-boswellic acid derivatives, and the synthetic analogs CDDO, CDODA and their esters decreased expression of specificity protein (Sp) transcription factors and several pro-oncogenic Sp-regulated genes in multiple cancer cell lines. The mechanisms of this response are both compound- and cell context-dependent and include activation of both proteasome-dependent and -independent pathways. Triterpenoid-mediated induction of reactive oxygen species (ROS) has now been characterized as an important proteasome-independent pathway for downregulation of Sp transcription factors. ROS decreases expression of microRNA-27a (miR-27a) and miR-20a/miR-...Continue Reading

Citations

May 16, 2014·Current Breast Cancer Reports·Beate C Litzenburger, Powel H Brown
Nov 15, 2014·Phytochemistry Reviews : Proceedings of the Phytochemical Society of Europe·Nisha R ParikhAnupam Bishayee
Jun 10, 2014·Expert Opinion on Therapeutic Patents·René Csuk
May 6, 2014·Expert Opinion on Therapeutic Targets·Stephen SafeIndira Jutooru
Oct 25, 2014·Natural Product Reports·Robert A Hill, Joseph D Connolly
Jan 27, 2015·European Journal of Medicinal Chemistry·René CsukAhmed Al-Harrasi
Nov 9, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li Xiao RuiTang Ze Yao
Jun 18, 2016·Journal of Asian Natural Products Research·Krishna ChallaG L David Krupadanam
Jan 2, 2015·Acta Crystallographica. Section E, Structure Reports Online·Wei TangYao-Lan Li
Nov 5, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Runlan LuoZeyao Tang
Feb 27, 2019·Current Pharmaceutical Biotechnology·Isabel Sánchez-CrisóstomoRosa A Bobadilla-Lugo
Oct 26, 2016·Molecular Medicine Reports·Xia ZhangYan Chen
Jul 10, 2020·Chemistry & Biodiversity·Luiza Stolz CruzFlávio Luís Beltrame
Mar 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Richard KomakechFrancis Omujal
Oct 14, 2020·European Journal of Medicinal Chemistry·Oliver KraftRené Csuk

❮ Previous
Next ❯

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.