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Published on: September 19, 2018
Alkyl isothiocyanates suppress epidermal growth factor receptor kinase activity but augment tyrosine kinase activity
Takahiro Nomura1, Yoshimasa Uehara, Hiroo Kawajiri
1Department of Food and Nutritional Science, Kanazawa Gakuin College, 10 Sue-machi, Kanazawa, Ishikawa 920-1392, Japan. nomurat@kanazawa-gu.ac.jp
Aim:
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.
Discussion:
A possible anticancer mechanism of MITCs may involve the suppression of EGF receptor kinase activity and augmentation of non-receptor PTK.
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