Inhibition of Hepatocyte Growth Factor Induction in Human Dermal Fibroblasts by Tryptanthrin(Pharmacology)
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概要
- 論文の詳細を見る
In addition to regulation of normal cell functions, hepatocyte growth factor (HGF) has also been shown to be involved in malignant cell transformation and in growth, invasion and metastasis in cancer cells. Inhibitors of HGF production have a potential for interfering with malignant cell transformation and progression of tumors. We found that tryptanthrin, one of the major compounds extracted from the medicinal plant Polygonum tinctorium, which is known for its antitumor activity, strongly inhibited HGF production stimulated by various HGF inducers in human dermal fibroblasts. HGF production induced by phorbol 12-myristate 13-acetate (PMA) was potently inhibited by tryptanthrin without any appreciable cytotoxic effect. Tryptanthrin also inhibited HGF production induced by epidermal growth factor (EGF) and platelet-derived growth factor. Moreover, proliferation of the fibroblasts induced by the two growth factors was potently suppressed by tryptanthrin to the level of proliferation of unstimulated fibroblasts. However, tryptanthrin did not inhibit HGF production induced by the protein kinase A-activating agents cholera toxin and 8-bromo-cAMP. These effects of tryptanthrin were different from the effects of transforming growth factor β1 and dexamethasone, both of which inhibit HGF production induced by all the above inducers. Upregulations of HGF gene expression by PMA and EGF were also inhibited by tryptanthrin. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway is crucial for PMA-induced HGF production, but tryptanthrin did not attenuate phosphorylation of MAPK induced by PMA. These results indicate that tryptanthrin potently inhibited induction of HGF production probably through events downstream of MAPK activation.
- 社団法人日本薬学会の論文
- 2005-02-01
著者
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Yamamoto Itaru
岡山大学 薬学部免疫医薬品化学
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Yagi Y
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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YAMAMOTO Itaru
Department of Radiology, Kanazawa Medical University
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Yamamoto I
Okayama Univ. Okayama Jpn
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TAI Akihiro
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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GOHDA Eiichi
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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MOTOKI Takahiro
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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TAKAMI Yoichiro
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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YAGI Yasuyuki
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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Yagi Yasuyuki
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Yamamoto Itaru
Department Of Immunochemistry Faculty Of Pharmaceutical Science Okayama University
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Tai A
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Tai Akihiro
Department Of Immunochemistry Division Of Pharmaceutical Sciences Okayama University Graduate School
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Gohda Eiichi
Dep. Of Immunochemistry Div. Of Pharmaceutical Sciences Okayama Univ. Graduate School Of Medicine De
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Gohda E
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Gohda Eiichi
Department Of Immunochemistry Division Of Pharmaceutical Sciences Okayama University Graduate School
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Takami Yoichiro
Department Of Digestive And Lifestyle-related Disease Health Research Human And Environmental Scienc
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Takami Yoichiro
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Yamamoto I
Department Of Immunochemistry Division Of Pharmaceutical Sciences Okayama University Graduate School
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Motoki Takahiro
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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GOHDA Eiichi
Department of Biochemistry, Faculty of Dentistry, Osaka University
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