title: 25-O-acetyl-23,24-dihydro-cucurbitacin F induces cell cycle G2/M arrest and apoptosis in human soft tissue sarcoma cells.
abstract: BACKGROUND
  Quisqualis indica is used in traditional Chinese medicine to treat cancer and related syndromes and also known for its anthelminthic effects.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our data strongly support 1 as a very interesting target for further investigation and development of novel therapeutics in sarcoma research.
authors.affiliation: Department of Orthopaedic Surgery, Medical University Graz, Auenbruggerplatz 5, 8036 Graz, Austria. Electronic address: birgit.lohberger@medunigraz.at.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, 8010 Graz, Austria.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kretschmer
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University Graz, Harrachgasse 21/3, 8010 Graz, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Bernhart
authors.affiliation: Center for Medical Research, Medical University Graz, Stiftingtalstrasse 24, 8010 Graz, Austria.
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.affiliation: Department of Orthopaedic Surgery, Medical University Graz, Auenbruggerplatz 5, 8036 Graz, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stuendl
authors.affiliation: Department of Orthopaedic Surgery, Medical University Graz, Auenbruggerplatz 5, 8036 Graz, Austria.
authors.forename: Heike
authors.initials: H
authors.lastname: Kaltenegger
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, 8010 Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kahl
authors.affiliation: Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, 8010 Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Department of Orthopaedic Surgery, Medical University Graz, Auenbruggerplatz 5, 8036 Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019925:Cyclin A / Q000235:genetics; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma; D000077022:Survivin; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C000604032:25-O-acetyl-23,24-dihydro-cucurbitacin F; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D019925:Cyclin A; D056744:Cyclin B1; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D014315:Triterpenes; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D053148:Caspase 3
keywords: 24-dihydro-cucurbitacin F; 25-O-acetyl-23; Apoptosis; Cell cycle; Quisqualis indica; Soft tissue sarcoma