Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A2-2 in Human Prostate Cancer Cells
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Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A2-2 in Human Prostate Cancer Cells. / Menchinskaya, Ekaterina S.; Dyshlovoy, Sergey A.; Venz, Simone; Jacobsen, Christine; Hauschild, Jessica; Rohlfing, Tina; Silchenko, Aleksandra S.; Avilov, Sergey A.; Balabanov, Stefan; Bokemeyer, Carsten; Aminin, Dmitry L.; von Amsberg, Gunhild; Honecker, Friedemann.
in: MAR DRUGS, Jahrgang 22, Nr. 1, 20, 28.12.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A2-2 in Human Prostate Cancer Cells
AU - Menchinskaya, Ekaterina S.
AU - Dyshlovoy, Sergey A.
AU - Venz, Simone
AU - Jacobsen, Christine
AU - Hauschild, Jessica
AU - Rohlfing, Tina
AU - Silchenko, Aleksandra S.
AU - Avilov, Sergey A.
AU - Balabanov, Stefan
AU - Bokemeyer, Carsten
AU - Aminin, Dmitry L.
AU - von Amsberg, Gunhild
AU - Honecker, Friedemann
PY - 2023/12/28
Y1 - 2023/12/28
N2 - 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.
AB - 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.
KW - cucumarioside A2-2
KW - castration-resistant prostate cancer
KW - PC-3 cells
KW - apoptosis
KW - anti-metastatic activity
KW - proteomics
U2 - 10.3390/md22010020
DO - 10.3390/md22010020
M3 - SCORING: Journal article
C2 - 38248645
VL - 22
JO - MAR DRUGS
JF - MAR DRUGS
SN - 1660-3397
IS - 1
M1 - 20
ER -
