Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A2-2 in Human Prostate Cancer Cells

Abstract

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A2-2 (CA2-2) using an in vitro CRPC model. CA2-2 induced a G2/M-phase cell cycle arrest in human prostate cancer PC-3 cells and caspase-dependent apoptosis executed via an intrinsic pathway. Additionally, the drug inhibited the formation and growth of CRPC cell colonies at low micromolar concentrations. A global proteome analysis performed using the 2D-PAGE technique, followed by MALDI-MS and bioinformatical evaluation, revealed alterations in the proteins involved in cellular processes such as metastatic potential, invasion, and apoptosis. Among others, the regulation of keratin 81, CrkII, IL-1β, and cathepsin B could be identified by our proteomics approach. The effects were validated on the protein level by a 2D Western blotting analysis. Our results demonstrate the promising anticancer activity of CA2-2 in a prostate cancer model and provide insights on the underlying mode of action.

The Composition of Triterpene Glycosides in the Sea Cucumber Psolus peronii: Anticancer Activity of the Glycosides against Three Human Breast Cancer Cell Lines and Quantitative Structure–Activity Relationships (QSAR)

“…Studies of triterpene glycosides, biosynthesized by the sea cucumbers, not only have fundamental scientific interest but also practical applications based on the diverse biological activity of these compounds. Some of them have demonstrated potential antitumor action against different human cancer cells in vitro, initiating apoptosis by diverse signaling pathways, inhibiting the adhesion, migration, invasion and angiogenesis of cancer cells [8][9][10][11][12][13][14][15], or can be used in cancer immunotherapy [16].…”