Planta Med 2010; 76 - P358
DOI: 10.1055/s-0030-1264656

Effects of dimethylacrylshikonin and epoxyshikonin on melanoma cell lines

N Kretschmer 1, B Rinner 2, A Deutsch 3, H Knausz 2, M Blunder 1, O Kunert 4, T Efferth 5, H Schaider 6, H Boechzelt 7, R Bauer 1
  • 1Karl-Franzens University, Institute of Pharmaceutical Sciences, Pharmacognosy, Universitätsplatz 4/1, 8010 Graz, Austria
  • 2Medical University, Center for Medical Research, Core Facility of Flow Cytometry, Stiftingtalstraße 24, 8010 Graz, Austria
  • 3Medical University, Internal Medicine, Hematology, Auenbruggerplatz 38, 8036 Graz, Austria
  • 4Karl-Franzens University, Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Universitätsplatz 1, 8010 Graz, Austria
  • 5University of Mainz, Institute of Pharmacy, Pharmaceutical Biology, Staudingerweg 5, 55099 Mainz, Germany
  • 6Cancer Biology Unit, Medical University, Dermatology and Center for Medical Research, Auenbruggerplatz 8, 8010 Graz, Austria
  • 7Joanneum Research Forschungsgesellschaft, Steyrergasse 17–19, 8010 Graz, Austria

Cancer is one of the most common causes of death worldwide. Much research has been performed on how to fight this disease. However, current therapeutic concepts have still limited effectiveness because of resistances of tumours and lethal side effects. Therefore, identifying and developing new anti-cancer drugs are still important research objectives. A petrol ether extract of Onosma paniculatum showed strong growth inhibition, cell cycle influence and activation of caspase 3 in melanoma cells from primary (SBc-L2, WM35) and metastatic (WM9, WM164) lesions [1]. We now isolated and identified the active compounds and started different pharmacological tests to reveal the mechanism of action. Four active shikonin derivatives were isolated using preparative HPLC. The two main compounds, dimethylacrylshikonin and epoxyshikonin, showed IC50 values of: SBc-L2: 1.1µM and 15.5µM; WM35: 2.3µM and 22.9µM; WM9: 2.7µM and 18.8µM; WM164: 8.3µM and 53.2µM, respectively. Their effects on cell cycle and appearance of a sub-G1 peak were analyzed by flow cytometry. Both increased the sub-G1 DNA content and the percentage of G2/M-phase cells, accompanied by a decrease of G1-phase cells. Moreover, in SBc-L2 and WM164 cells, the influence of dimethylacrylshikonin on expression levels of different apoptosis involved genes were examined using real-time PCR. In SBc-L2 cells, expression of extrinsic (Fas-Ligand, Trail) and intrinsic (Bim, noxa, bid) apoptotic genes were induced, whereas, in WM164, only intrinsic apoptotic genes (bmf, noxa, bik, bax) where induced. Our data suggest that dimethylacrylshikonin and epoxyshikonin inhibit cell growth of tumor cells and may ultimately lead to cell death through apoptosis induction.

Acknowledgements: This work was supported by the „Fonds zur Foerderung der Wissenschaftlichen Forschung“ P21114.

References: 1. Rinner, B. et al. (2010)J Ethnopharmacol. in press.