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Lohberger, B; Kretschmer, N; Bernhart, E; Rinner, B; Stuendl, N; Kaltenegger, H; Kahl, S; Bauer, R; Leithner, A.
25-O-acetyl-23,24-dihydro-cucurbitacin F induces cell cycle G2/M arrest and apoptosis in human soft tissue sarcoma cells.
J Ethnopharmacol. 2015; 164(3):265-272
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Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Kaltenegger Heike
Leithner Andreas
Lohberger Birgit
Rinner Beate
Stündl Nicole
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Abstract:
Quisqualis indica is used in traditional Chinese medicine to treat cancer and related syndromes and also known for its anthelminthic effects. Soft tissue sarcomas represent a rare group of malignant tumors that frequently exhibit chemotherapeutic resistance and increased metastatic potential. In this study, we evaluated the cytotoxic, apoptosis inducing and cell cycle arresting effects of 25-O-acetyl-23,24-dihydro-cucurbitacin F which has been isolated from leaves and twigs of Q. indica. The present study investigates the effects of 25-O-acetyl-23,24-dihydro-cucurbitacin F (1) on cell viability, cell cycle distribution, and apoptotic induction of three human sarcoma cell lines of various origins by using the CellTiter 96(®) AQueous One Solution Cell Proliferation Assay, flow cytometrical experiments, real-time RT-PCR, Western blotting, and the Caspase-Glo(®) 3/7 Assay We could show that 1 reduced cell viability in a dose-dependent manner and arrested the cells at the G2/M interface. The accumulation of cells at the G2/M phase resulted in a significant decrease of the cell cycle checkpoint regulators cyclin B1, cyclin A, CDK1, and CDK2. Interestingly, 1 inhibited survivin expression significantly, which functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types including sarcomas. Moreover, 1 induced apoptosis in liposarcoma and rhabdomyosarcoma cells caspase-3 dependently. Our data strongly support 1 as a very interesting target for further investigation and development of novel therapeutics in sarcoma research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
CDC2 Protein Kinase -
Caspase 3 - metabolism
Cell Line, Tumor -
Cell Survival - drug effects
Cyclin A - genetics
Cyclin B1 - genetics
Cyclin B1 - metabolism
Cyclin-Dependent Kinase 2 - genetics
Cyclin-Dependent Kinase 2 - metabolism
Cyclin-Dependent Kinases - genetics
Cyclin-Dependent Kinases - metabolism
G2 Phase Cell Cycle Checkpoints - drug effects
Humans -
Inhibitor of Apoptosis Proteins - genetics
Inhibitor of Apoptosis Proteins - metabolism
Sarcoma -
Survivin -
Triterpenes - pharmacology

Find related publications in this database (Keywords)
25-O-acetyl-23
24-dihydro-cucurbitacin F
Soft tissue sarcoma
Cell cycle
Apoptosis
Quisqualis indica
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