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Alkyl isothiocyanates suppress epidermal growth factor receptor kinase activity but augment tyrosine kinase activity
Authors:Takahiro Nomura  Yoshimasa Uehara  Hiroo Kawajiri  Kazuo Ryoyama  Takao Yamori  Yoko Fuke
Affiliation:1. Department of Food and Nutritional Science, Kanazawa Gakuin College, 10 Sue-machi, Kanazawa, Ishikawa 920-1392, Japan;2. Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan;3. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, Aomori, Japan;4. Cancer Chemotherapy Center, Cancer Research Institute of Japanese Cancer Association, Tokyo, Japan;5. Department of Food Science and Human Nutrition, Tokyo Metropolitan University, Tokyo, Japan;1. Leibniz-Institute of Vegetable and Ornamental Crops Grossbeeren/Erfurt e.V., Theodor-Echtermeyer-Weg 1, 14979 Grossbeeren, Germany;2. Technische Universität Berlin, Institute of Food Technology and Food Chemistry, Gustav-Meyer-Allee 25, 13355 Berlin, Germany;3. Universität Hamburg, Institute of Food Chemistry, Grindelallee 117, 20146 Hamburg, Germany;1. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China;2. Department of Cardiology, Shandong Energy Zibo Mining Group Co., Ltd Central Hospital, Zibo 255120, China;3. Department of Center Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China;4. Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China;1. Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China;2. Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China;3. University of Chinese Academy of Sciences, Beijing 100049, China
Abstract:
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 μg/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.
Keywords:
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