Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A<sub>2</sub>-2 in Human Prostate Cancer Cells
Ekaterina S. Menchinskaya,
Sergey A. Dyshlovoy,
Simone Venz,
Christine Jacobsen,
Jessica Hauschild,
Tina Rohlfing,
Aleksandra S. Silchenko,
Sergey A. Avilov,
Stefan Balabanov,
Carsten Bokemeyer,
Dmitry L. Aminin,
Gunhild von Amsberg,
Friedemann Honecker
Affiliations
Ekaterina S. Menchinskaya
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Sergey A. Dyshlovoy
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Simone Venz
Department of Medical Biochemistry and Molecular Biology, University of Greifswald, 17475 Greifswald, Germany
Christine Jacobsen
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Jessica Hauschild
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Tina Rohlfing
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Aleksandra S. Silchenko
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, Russia
Sergey A. Avilov
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, Russia
Stefan Balabanov
Division of Hematology, University Hospital Zurich, 8091 Zurich, Switzerland
Carsten Bokemeyer
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Dmitry L. Aminin
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, Russia
Gunhild von Amsberg
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Friedemann Honecker
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
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.
