Alkyl isothiocyanates suppress epidermal growth factor receptor kinase activity but augment tyrosine kinase activity.
OBJECTIVE
We have reported the in vitro and in vivo anticancer activities of 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) derived from a Japanese spice, wasabi. In order to obtain some clues about the mechanism of the anticancer activity, we have studied the effect of alkyl isothiocyanates (MITCs) on protein kinase activities.


METHODS
The anti-autophosphorylation activity of MITCs with respect to the epidermal growth factor (EGF)-stimulated receptor kinase of A431 epidermoid carcinoma cells was examined by incorporation of radioactive ATP into an acid-insoluble fraction. Their anti-phosphorylation activity with respect to the non-receptor protein kinase was analyzed by a standard SDS-PAGE method.


RESULTS
All the tested MITCs interfered with the EGF-stimulated receptor kinase activity in a dose-dependent manner, although their effects were less than 1/10 of that of erbstatin in microg/ml. On the other hand, the MITCs did not interfere with non-receptor kinases (kinase A, kinase C, tyrosine kinase and calmodulin dependent kinase III), but enhanced non-receptor tyrosine kinase.


CONCLUSIONS
A possible anticancer mechanism of MITCs may involve the suppression of EGF receptor kinase activity and augmentation of non-receptor PTK.
Nomura
Takahiro
T
Department of Food and Nutritional Science, Kanazawa Gakuin College, 10 Sue-machi, Kanazawa, Ishikawa 920-1392, Japan. nomurat@kanazawa-gu.ac.jp
Uehara
Yoshimasa
Y
Kawajiri
Hiroo
H
Ryoyama
Kazuo
K
Yamori
Takao
T
Fuke
Yoko
Y
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D017879:Isothiocyanates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D006873:Hydroquinones; D017879:Isothiocyanates; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C048212:erbstatin