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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(36):265-272
Doi: 10.1016/j.jep.2015.02.023
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
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Lohberger Birgit
- Co-Autor*innen der Med Uni Graz
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Bernhart Eva Maria
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Eck Nicole
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Kaltenegger Heike
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Kretschmer Nadine
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Leithner Andreas
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Rinner Beate
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- Abstract:
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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)
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Antineoplastic Agents - pharmacology
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Apoptosis - drug effects
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CDC2 Protein Kinase -
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Caspase 3 - metabolism
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Cell Line, Tumor -
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Cell Survival - drug effects
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Cyclin A - genetics
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Cyclin B1 - genetics
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Cyclin B1 - metabolism
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Cyclin-Dependent Kinase 2 - genetics
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Cyclin-Dependent Kinase 2 - metabolism
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Cyclin-Dependent Kinases - genetics
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Cyclin-Dependent Kinases - metabolism
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G2 Phase Cell Cycle Checkpoints - drug effects
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Humans -
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Inhibitor of Apoptosis Proteins - genetics
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Inhibitor of Apoptosis Proteins - metabolism
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Sarcoma -
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Survivin -
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Triterpenes - pharmacology
- Find related publications in this database (Keywords)
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25-O-acetyl-23
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24-dihydro-cucurbitacin F
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Soft tissue sarcoma
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Cell cycle
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Apoptosis
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Quisqualis indica