Planta Med 2015; 81 - PM_205
DOI: 10.1055/s-0035-1565582

Effects of 25-O-acetyl-23,24-dihydro-cucurbitacin F on cell viability, cell cycle distribution and apoptosis induction in human soft tissue sarcoma cells

N Kretschmer 1, 4, B Lohberger 2, E Bernhart 3, B Rinner 4, N Stuendl 2, H Kaltenegger 2, S Kahl 1, R Bauer 1, A Leithner 2
  • 1Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria
  • 2Department of Orthopaedic Surgery, Medical University Graz, Graz, Austria
  • 3Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria
  • 4Center for Medical Research, Medical University Graz, Graz, Austria

Soft tissue sarcomas represent a rare group of malignant tumors frequently exhibiting increased metastatic potential and chemotherapeutic resistance. Treatment is often unsuccessful or the efficacy limited. Therefore, there is an urgent need for the discovery of new lead compounds. In this study, we investigated the effects of 25-O-acetyl-23,24-dihydro-cucurbitacin F (ADCF) on cell viability, cell cycle distribution and apoptosis induction in three different sarcoma cell lines. The compound was previously isolated as most active constituent from Quisqualis indica L. (Combretaceae) which gained interest as a result of a systematic bioactivity-based screening of plants used in traditional Chinese medicine [1]. In soft tissue sarcoma cells, ADCF reduced cell viability concentration dependently (IC50 values after 48h: SW-872: 16.2 µM; SW-982: 4.3 µM; TE-671: 1.2 µM). In SW-872 and TE-671 cells, ADCF additionally arrested the cells at the G2/M interphase and led to a significant reduction of cyclin B1, cyclin A, CDK1, CDK2 and survivin. Moreover, it induced apoptosis caspase-3 dependently [2]. However, in SW-982 cells, the cell cycle was only slightly changed and caspase-3 was not activated when treated with the IC50.

Acknowledgements: This work was supported by the Austrian Science Fund (P 27505) and the Medical University of Graz.

References:

[1] Efferth T, Kahl S, Paulus K, Adams M, Rauh R, Boechzelt H, Hao X, Kaina B, Bauer R. Phytochemistry and pharmacogenomics of natural products derived from traditional Chinese medicine and Chinese materia medica with activity against tumor cells. Mol Cancer Ther 2008; 7: 152 – 161

[2] 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: 265 – 272