Highlights of pentacyclic triterpenes in the cancer setting

Pentacyclic triterpenoid acids including oleanolic, betulinic and ursolic acids and their derivatives, exhibit a wide spectrum of anticancer activities and these include activation of growth inhibitory, proapoptotic and antiangiogenic pathways. Induction of these and other responses undoubtedly involves multiple mechanisms of action; however, it is possible that a more limited number of activities may contribute to their antitumorigenic activity. Studies in this laboratory have demonstrated that several triterpenoid acids or their esters downregulate expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in several cancer cell lines and tumors. Moreover, decreased expression of Sp proteins is accompanied by decreased expression of Sp-dependent genes associated with growth (cyclin D1 and epidermal growth factor receptor), survival (survivin), and angiogenesis (vascular endothelial growth factor and its receptors). These results demonstrate that an important mechanism of action for triterpenoid acids as anticancer drugs is associated with their downregulation of Sp transcription factors.