Cytotoxic and Apoptosis-Inducing Activity of Triterpene Glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 Cells

Abstract

The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell lines were detected and their cytotoxicity-structure relationships were established. The apoptosis-inducing activity of a more potent glycoside echinoside A (1) in HepG2 cells was further investigated by determining its effect on the morphology, mitochondrial transmembrane potential (Δψm) and mRNA expression levels of the apoptosis-related genes. The results showed that the number of glycosyl residues in sugar chains and the side chain of aglycone could affect their cytotoxicity towards tumor cells and selective cytotoxicity. 1 significantly inhibited cell viability and induced apoptosis in HepG2 cells. 1 also markedly decreased the Δψm and Bcl-2/Bax mRNA express ratio, and up-regulated the mRNA expression levels of Caspase-3, Caspase-8 and Caspase-9 in HepG2 cells. Therefore, 1 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathway. These findings could potentially promote the usage of these glycosides as leading compounds for developing new antitumor drugs.

Three New Cytotoxic Polyhydroxysteroidal Glycosides from Starfish Craspidaster hesperus

“…Steroidal metabolites from starfish, especially steroidal oligoglycosides, were reported to show a broad spectrum of biological activities, including cytotoxic, hemolytic, antiviral, antibacterial, antibiofouling, neuritogenic, and antifungal effects [1,7,8,9,10]. As a continuation of our previous studies on biologically active compounds from echinoderms [11,12,13,14], we collected starfish Craspidaster hesperus from the South China Sea, and evaluated biological activity of the steroidal glycosides from this starfish. To our knowledge, the polyhydroxysteroidal glycosides from C. hesperus remains unknown, although some polyhydroxysteroidal glycosides from other starfish (e.g., Anthenea chinensis ) , were reported [15].…”

Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway

“…The administration of uvaol produced a decrease in the levels of this anti-apoptotic protein in the cancer line, a result that is consistent with the induction of cell death due to apoptosis, and the arrest in the G 0 /G 1 phase obtained in our findings. Other triterpenes have been reported to also induce apoptosis in HepG2 cells through a down-regulation in Bcl-2 [ 40 ]. Similar results have been also found in other cancer cell lines, such as HT29 [ 41 ].…”

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties

“…The mechanism by which triterpene glycosides exhibit anticancer activity primarily involve induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G 2 /M phases and increase of the sub-G 0 /G 1 cell population; regulation of nuclear factor NF-κB expression; reduction in cancer cell adhesion; suppression of cell migration and tube formation; suppression of angiogenesis; inhibition of cell proliferation, colony formation, and tumor invasion [141]. However, the detailed mechanism(s) of the anticancer activities of these glycosides remains largely unclear.…”