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 Apr 22:164:265-72. doi: 10.1016/j.jep.2015.02.023.
Birgit Lohberger  1 ,  Nadine Kretschmer  2 ,  Eva Bernhart  3 ,  Beate Rinner  4 ,  Nicole Stuendl  5 ,  Heike Kaltenegger  5 ,  Stefan Kahl  2 ,  Rudolf Bauer  2 ,  Andreas Leithner  5
Affiliations
  • 1. Department of Orthopaedic Surgery, Medical University Graz, Auenbruggerplatz 5, 8036 Graz, Austria. Electronic address: [email protected].
  • 2. Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4/1, 8010 Graz, Austria.
  • 3. Institute of Molecular Biology and Biochemistry, Medical University Graz, Harrachgasse 21/3, 8010 Graz, Austria.
  • 4. Center for Medical Research, Medical University Graz, Stiftingtalstrasse 24, 8010 Graz, Austria.
  • 5. Department of Orthopaedic Surgery, Medical University Graz, Auenbruggerplatz 5, 8036 Graz, Austria.
PMID: 25701753 DOI: 10.1016/j.jep.2015.02.023
Abstract

Ethnopharmacological relevance: Quisqualis indica is used in traditional Chinese medicine to treat Cancer and related syndromes and also known for its anthelminthic effects.

Aim of the study: 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.

Material and 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.

Conclusion: Our data strongly support 1 as a very interesting target for further investigation and development of novel therapeutics in sarcoma research.

Keywords
24-dihydro-cucurbitacin F; 25-O-acetyl-23; Apoptosis; Cell cycle; Quisqualis indica; Soft tissue sarcoma.
Products