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


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 43 microg/ml (corresponding to 1.3mg/ml of dried plant material) which correlated with cyclin D1- and Cdc25A suppression and p21 induction. At 132 microg/ml (=4 mg/ml of the drug) this extract caused genotoxic stress indicated by substantial phosphorylation of the core histone H2AX (gamma-H2AX) followed by activation of caspase 3 and signature-type cleavage of PARP resulting in a 55% apoptosis rate after 48 hours 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.
Ozmen
Ali
A
Institute of Biology, Fen-Edebiyat Fakültesi, Adnan Menderes Universitesi, Aydin, Turkey.
Madlener
Sibylle
S
Bauer
Sabine
S
Krasteva
Stanimira
S
Vonach
Caroline
C
Giessrigl
Benedikt
B
Gridling
Manuela
M
Viola
Katharina
K
Stark
Nicole
N
Saiko
Philipp
P
Michel
Barbara
B
Fritzer-Szekeres
Monika
M
Szekeres
Thomas
T
Askin-Celik
Tülay
T
Krenn
Liselotte
L
Krupitza
Georg
G
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D031363:Scutellaria / Q000737:chemistry*; D014421:Turkey; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D010936:Plant Extracts; D019938:Cyclin D1; D011065:Poly(ADP-ribose) Polymerases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D053148:Caspase 3