Chapter 2 - Sea Cucumber Triterpene Glycosides as Anticancer Agents

Abstract

Abstract Triterpene glycosides are natural low molecular weight compounds that are widespread in terrestrial plants and some sea animals. Among them holothurians (sea cucumbers) are a rich source of triterpene glycosides with diverse chemical structures and physiological activities. In recent years, researchers attention was attracted not only well-studied cytotoxic properties of triterpene glycosides of sea cucumbers but also their ability to suppress the growth of various malignant tumors in experimental animals. It has been found that these natural products are able to retard cancer cell proliferation and arrest cancer cell cycle at different stages that inhibit tumor progression, induce tumor cell apoptosis through the different pathways, which finally lead to programmed cell death. It was noted that some glycosides can affect cancer cell motility, which is expressed in reduction of cell adhesion, suppression of cytoskeleton reorganization, cell migration, and colony formation. Some sea cucumber glycosides were discovered to suppress the angiogenesis of blood vessels that may disturb the tumor sustentation and feeding. All this leads to significant limitation of tumor development, invasion, and metastasis. The recent detailed study of molecular basis of anticancer activity of holothurians triterpene glycosides demonstrates that these compounds can regulate nuclear factor, NF-κB, a key player linking chronic inflammation and cancer, affecting the certain cellular receptors and enzymes participating in cancerogenesis, such as epithelial growth factor receptors, different kinases (protein kinase B, extracellular signal-regulated kinase, focal adhesion kinase, and so on), matrix metalloproteinase, and others. Furthermore, some holothurian triterpene glycosides have a tendency to inhibit the cancer cell multidrug resistance (MDR) and therefore could be used as P-gp-mediated MDR reversal agent in combined ant-cancer therapy with standard cytostatics. This review contains virtually all the recent updated and detailed information regarding cytotoxic, cancer-preventive effects, and antitumor activity of holothurians triterpene glycosides.