Oridonin Inhibited the Tyrosine Kinase Activity and Induced Apoptosis in Human Epidermoid Carcinoma A431 Cells(Molecular and Cell Biology)

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概要

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• Oridonin, an active component isolated from the plant Rabdosia rubescens, has been reported to exhibit antitumor effects, but little is known about its molecular mechanism of action. In this study, we first investigated the mechanism involved in oridonin-induced cell death in human epidermoid carcinoma A431 cells, which overexpress epidermal growth factor receptor (EGFR). After treatment with various doses of oridonin for 24h, the majority of A431 cells underwent apoptosis in a time- and dose-dependent manner as measured by an LDH activity-based assay. Treatment with oridonin at various concentrations for 24h caused significant inhibition on the total tyrosine kinase activities and downregulation of EGFR expression or EGFR phosphorylation. Oridonin significantly affected the localization of EGFR and phosphorylated EGFR on the cell membrane. However, genistein (a well-known tyrosine kinase inhibitor) did not induce apoptotic A431 cell death. Importantly, oridonin exhibited much stronger inhibitory effect on the total tyrosine kinase activities or EGFR tyrosine phosphorylation as well as much stronger suppression on EGFR and phosphorylated EGFR localization than genistein in A431 cells. Taken together, oridonin exerted a potential inhibitory effect on the tyrosine kinase activity of A431 cells. The decrease in the tyrosine kinase activity and the blockage of EGFR tyrosine phosphorylation might be one of the causes of oridonin-induced A431 cell death.

• 社団法人日本薬学会の論文
• 2007-02-01

著者

• Tashiro Shin-ichi

  Dep. Of Clinical And Biomedical Sciences Showa Pharmaceutical Univ. Jpn

• TASHIRO Shin-ichi

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• ONODERA Satoshi

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• IKEJIMA Takashi

  China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical Unive

• Wu Li-jun

  Department Of Phytochemistry Shenyang Pharmaceutical University

• Wu L

  Department Of Phytochemistry Shenyang Pharmaceutical University

• Onodera S

  Dep. Of Clinical And Biomedical Sciences Showa Pharmaceutical Univ. Jpn

• Onodera Satoshi

  昭和薬科大学 病態科

• Ikejima Takashi

  China-japan Res. Inst. Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical Univ. Chn

• LI Dan

  China-Japan Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University

• Tashiro Shin-ichi

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Onodera Satoshi

  Department Of Cinical And Biomedical Sciences Showa Pharmaceutical University

• Tashiro Shin-ichi

  Department Of Cinical And Biomedical Sciences Showa Pharmaceutical University

• Li Dan

  China-japan Research Institute Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical Univer

• Tashiro S

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Onodera S

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Ikejima Takashi

  China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University

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