In vitro anti-leukemic activity of the ethno-pharmacological plant Scutellaria orientalis ssp. carica endemic to western Turkey

Özmen, Ali; Madlener, Sibylle; Bauer, Sabine; Krasteva, Stanimira; Vonach, Caroline; Giessrigl, Benedikt; Gridling, Manuela; Viola, Katharina; Stark, Nicole; Saiko, Philipp; Michel, Barbara; Fritzer-Szekeres, Monika; Szekeres, Thomas; Askin-Celik, Tülay; Krenn, Liselotte; Krupitza, Georg

doi:10.1016/j.phymed.2009.06.001

« Previous Next »Phytomedicine
Volume 17, Issue 1 , Pages 55-62, January 2010

In vitro anti-leukemic activity of the ethno-pharmacological plant Scutellaria orientalis ssp. carica endemic to western Turkey

Ali Özmen
- Institute of Biology, Fen-Edebiyat Fakültesi, Adnan Menderes Üniversitesi, Aydin, Turkey
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Sibylle Madlener
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Sabine Bauer
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Stanimira Krasteva
- Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Austria
Caroline Vonach
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Benedikt Giessrigl
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Manuela Gridling
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Katharina Viola
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Nicole Stark
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Philipp Saiko
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
Barbara Michel
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
Monika Fritzer-Szekeres
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
Thomas Szekeres
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
Tülay Askin-Celik
- Institute of Biology, Fen-Edebiyat Fakültesi, Adnan Menderes Üniversitesi, Aydin, Turkey
Liselotte Krenn
- Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Austria
Georg Krupitza
- Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
- Corresponding author. Tel.: +431404003487; fax: +431404003707.

published online 24 July 2009.

Abstract

Aim of this study

Within the genus Scutellaria various species are used in different folk medicines throughout Asia. Traditional Chinese Medicine (TCM) uses S. baicalensis (Labiatae) to treat various inflammatory conditions. The root shows strong anticancer properties in vitro and was suggested for clinical trials against multiple myeloma. Further, S. barbata was successfully tested against metastatic breast cancer in a phase I/II trial. Therefore, we investigated the anti-cancer properties of S. orientalis L. ssp. carica Edmondson, an endemic subspecies from the traditional medicinal plant S. orientalis L. in Turkey, which is used to promote wound healing and to stop haemorrhage.

Materials and methods

Freeze-dried plant material was extracted with petroleum ether, dichloromethane, ethyl acetate, and methanol and the bioactivity of these extracts was analysed by proliferation assay, cell death determination, and by investigating protein expression profiles specific for cell cycle arrest and apoptosis.

Results

The strongest anti-leukemic activity was shown by the methanol extract, which contained apigenin, baicalein, chrysin, luteolin and wogonin, with an IpC50 of 43μg/ml (corresponding to 1.3mg/ml of dried plant material) which correlated with cyclin D1- and Cdc25A suppression and p21 induction. At 132μg/ml (=4mg/ml of the drug) this extract caused genotoxic stress indicated by substantial phosphorylation of the core histone H2AX (γ-H2AX) followed by activation of caspase 3 and signature-type cleavage of PARP resulting in a 55% apoptosis rate after 48hours of treatment.

Conclusions

Here, we report for the first time that S. orientalis L. ssp. carica Edmondson exhibited potent anti-leukaemic properties likely through the anti-proliferative effect of baicalein and the genotoxic property of wogonin.

Keywords: Scutellaria orientalis ssp. carica, Leukemia, Apoptosis, Cell cycle inhibition, γ-H2AX