Reversal of P-Glycoprotein-Dependent Resistance to Vinblastine by Newly Synthesized Bisbenzylisoquinoline Alkaloids in Mouse Leukemia P388 Cells(Pharmacology)
スポンサーリンク
概要
- 論文の詳細を見る
We examined the ability of partially synthesized new compounds from fangchinoline and tetrandrine to reverse P-glycoprotein (P-gp)-dependent multidrug resistance (MDR) in vitro and in vivo. All compound enhanced the in vitro cyctotoxic effect of vinblastin (VBL) at 0.1μM as potent as 10μM verapamil against the resistant cell line P388/ADR. The combination effect tended to be strong by substitution of bulky group, resulting 5, 14-dibromotetrandrine (compound #9) showed the strongest effect. Compound #9 increased intracellular VBL accumulation in P388/ADR cells, much stronger than verapamil, as well as cytotoxic combined effect. This mechanism seems to inhibit the function of P-gp, but not the expression of P-gp. In combination with VBL, this compound also synergistically prolonged the life-span of P388/ADR-bearing mice. Bisbenzylisoquinoline alkaloids and their derivatives are possible to be good candidates as modifier of MDR in cancer chemotherapy.
- 公益社団法人日本薬学会の論文
- 2005-10-01
著者
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NOMURA Masaaki
Department of Pharmacology and Pharmaceutics, Graduate School of Natural Science and Technology, Kan
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MIYAMOTO Kenichi
Department of Medical Genetics, Ehime University School of Medicine
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Nomura Masaaki
北陸大学 薬学部臨床薬理学
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Wang F‐p
Sichuan Univ. Chengdu Chn
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Miyamoto Ken-ichi
Dep. Of Clinical Pharmacy Graduate School Of Natural Sci. And Technol. Kanazawa Univ.
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Nomura Masaaki
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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Wang Feng-peng
Dep. Of Chemistry Of Medicinal Natural Products West China Coll. Of Pharmacy Sichuan Univ.
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Nomura Masaaki
Department Of Hospital Pharmacy School Of Medicine Kanazawa University:department Of Clinical Pharma
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YANG Jin
Department of Geriatric, Medicine, Osaka University Medical School
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Yang Jin
Department Of Geriatric Medicine Osaka University Medical School
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Yang Jin
Department Of Natural Organic Chemistry School Of Pharmacy West China University Of Medical Sciences
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Yang Jin-song
Department Of Chemistry Of Medicinal Natural Products School Of Pharmacy West China University Of Me
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WANG Feng
Department of Chemistry of Medicinal Natural Products, West China College of Pharmacy, Sichuan Unive
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Miyamoto Kenichi
Department Of Hospital Pharmacy And Department Of Medicinal Informatics Graduate School Of Medical S
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Miyaamoto Ken-ichi
Department Of Medical Informatics Graduate School Of Medical Science Kanazawa University
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WANG Li
The National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine, Sichuan Universit
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Miyamoto K
Kanazawa Univ. Hospital Ishikawa Jpn
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Wang Feng-peng
Department Of Chemistry Of Medicinal Natural Products And Key Laboratory Of Drug Targeting Of Educat
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Yang Jin
Department Of Geriatric Medicine Osaka University Graduate School Of Medicine
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Miyamoto Kenichi
Department Of Chemistry For Materials Faculty Of Engineering And Graduate School Of Engineering Mie
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Miyamoto Kenichi
Department Of Hospital Pharmacy School Of Medicine Kanazawa University
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Yang Jin
Department Of Applied Chemistry Faculty Of Engineering Seikei University
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Wang Li
The National Chengdu Center For Safety Evaluation Of Traditional Chinese Medicine Sichuan University
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Wang Feng
Department Of Chemistry And Material Engineering Faculty Of Engineering Shinshu University
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Wang Feng-Peng
Deparmtment of Chemistry of Medicinal Natural Products, West China College of Pharmacy, Sichuan University
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