Compounds isolated from Psoralea corylifolia seeds inhibit protein kinase activity and induce apoptotic cell death in mammalian cells.
OBJECTIVE
Psoralea corylifolia is a plant widely used in traditional Chinese medicine, e.g. for its chemopreventive effect. To identify active substances responsible for this effect, we investigated pharmacological effects of 11 compounds isolated from the seeds of this plant (newly described substances: 7, 2', 4'-trihydroxy-3-arylcoumarin and psoracoumestan).


METHODS
The influence of distinct compounds on different signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) was screened via analysis of the activity of 24 protein kinases, mitogen activated protein kinase phosphorylation via Western blot, cytotoxicity was shown using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and determination of caspase activity. Oxidative stress was detected via 2',7'-dichlorofluorescein fluorescence.


RESULTS
Some compounds showed cytotoxic effects (H4IIE, Hct116, C6 cells) mainly mediated via induction of apoptosis. Distinct compounds caused a strong inhibition of MAPK/ERK kinase (MEK) phosphorylation, weak effects on extracellular-signal regulated kinase (ERK) phosphorylation and no significant effect on p38 and c-Jun amino-terminal kinase. Corylifol C and, to a lesser extent, xanthoangelol are potent protein kinase inhibitors (inhibitory concentration 50% values for epidermal growth factor receptor (EGFR): 1.1 and 4.4 × 10(-6)  μg/ml, respectively). Because EGFR, MEK and ERK are kinases involved in cellular proliferation, an inhibition of these enzymes may be useful to cause chemopreventive effects.


CONCLUSIONS
Distinct compounds isolated from P. corylifolia showed a high potential to influence cellular pathways, e.g. by inhibition of protein kinases that may be interesting for pharmacological purposes.
Institute of Toxicology, Heinrich-Heine-Universität, Düsseldorf, Germany.
Christian
C
Limper
Yao
Y
Wang
Sven
S
Ruhl
Zhiqiang
Z
Wang
Yijia
Y
Lou
Frank
F
Totzke
Michael H G
MH
Kubbutat
Yvonni
Y
Chovolou
Peter
P
Proksch
Wim
W
Wätjen
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002599:Chalcone / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D029907:Psoralea / Q000737:chemistry*; D051381:Rats; D012639:Seeds / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D002599:Chalcone; C068244:xanthoangelol; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases
apoptosis; cancer; cytotoxicity; kinase inhibitor; oxidative stress