Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer

Abstract

a b s t r a c tOver the last two decades, extensive research on plant-based medicinal compounds has revealed exciting and important pharmacological properties and activities of triterpenoids. Fruits, vegetables, cereals, pulses, herbs and medicinal plants are all considered to be biological sources of these triterpenoids, which have attracted great attention especially for their potent anti-inflammatory and anti-cancer activities. Published reports in the past have described the molecular mechanism(s) underlying the various biological activities of triterpenoids which range from inhibition of acute and chronic inflammation, inhibition of tumor cell proliferation, induction of apoptosis, suppression of angiogenesis and metastasis. However systematic analysis of various pharmacological properties of these important classes of compounds has not been done. In this review, we describe in detail the pre-clinical chemopreventive and therapeutic properties of selected triterpenoids that inhibit multiple intracellular signaling molecules and transcription factors involved in the initiation, progression and promotion of various cancers. Molecular targets modulated by these triterpenoids comprise, cytokines, chemokines, reactive oxygen intermediates, oncogenes, inflammatory enzymes such as COX-2, 5-LOX and MMPs, anti-apoptotic proteins, transcription factors such as NF-jB, STAT3, AP-1, CREB, and Nrf2 (nuclear factor erythroid 2-related factor) that regulate tumor cell proliferation, transformation, survival, invasion, angiogenesis, metastasis, chemoresistance and radioresistance. Finally, this review also analyzes the potential role of novel synthetic triterpenoids identified recently which mimic natural triterpenoids in physical and chemical properties and are moving rapidly from bench to bedside research.

Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies

“…Recent evidences have supported the beneficial effects of ursolic acid in a variety of human diseases, including various types of inflammation-driven cancers [11]. Anti-inflammatory and antiproliferative, proapoptotic, antimetastatic and antiangiogenic potential of ursolic acid have been reported in both in vitro and in vivo models of cancer [7]. Many preclinical efficacy studies using Discovery of bioactive molecules and elucidation of their molecular mechanisms open up an enormous opportunity for the development of improved therapy for different inflammatory diseases, including cancer.…”

“…Decades of research have provided ample evidence that the triterpenoids are multi-faceted in their molecular mechanism(s) as they modulate multiple targets and multiple pathways [7] (Fig. 1).…”

“…Decades of research on natural product agents that inhibit or deregulate this pathway have provided ample evidence that numerous dietary constituents and nutraceuticals may have antiinflammatory and chemopreventive effects [7,26]. In vitro studies using a variety of tumor cell lines have demonstrated the usefulness of ursolic acid in chemoprevention and in the treatment of inflammation-driven disease (Table 1).…”

“…chemically induced, subcutaneous and orthotopic human xenograft models and recently developed spontaneously developing transgenic tumor growth models have provided ample evidence that naturally occurring and synthetic derivatives of ursolic acid have chemopreventive and therapeutic properties [7]. Here, we discuss in detail the potential of ursolic acid as a chemopreventive and anticancer drug and its reported beneficial effects based on these preclinical and clinical investigations.…”

“…These emphasize the potential of various plant-derived cyclosqualenoid molecules to be used as anti-inflammatory, anticancer and antimicrobial agents [5]. Among various terpenoids, pentacyclic triterpenoids have been shown from various studies to be having wide ranging anti-inflammatory, chemopreventive, and anticancer activities and have been extensively studied previously [6][7][8][9].…”