2007 Fiscal Year Final Research Report Summary
Development of reversing agent for multidrug resistance and new chemotherapy by utilizing genistein
| Project/Area Number |
18590162
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Hiroshima International University |
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Principal Investigator |
MURAKAMI Teruo Hiroshima International University, Faculty of Pharmaceutical Sciences, Professor (20136055)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Nobuhiro Hiroshima International University, Faculty of Pharmaceutical Sciences, Associate Professor (70412351)
UNE Mizuho Hiroshima International University, Faculty of Pharmaceutical Sciences, Professor (20144826)
TOMOHARU Yokooji Hiroshima International University, Faculty of Pharmaceutical Sciences, Lecturer (70389120)
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| Project Period (FY) |
2006 – 2007
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| Keywords | ABC transporter / reversing agent for multidrug resistance / flavone / isoflavone / P-glycoprotein / MRP2 / pharmacokinetics / natural products |
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| Research Abstract |
In the present study, we examined the usefulness of natural products origin, genistein, as a reversing agent of multidrug resistance. Genistein itself is known to have an anticancer activity for breast cancer. Also, various soy products such as miso, tofu and so on contain genistein. Multidrug resistance of various cancer cells is known to be due to the induction of ABC efflux transporters that expel the substrate drugs such as anticancer agents out of cells. ABC efflux transporters involve P-glycoprotein, MRPs and BCRP. In the present study, genistein was found to have suppressing potency for P-gp function, though it has been recognized to suppress MRPs. When genistein was administered orally, the blood level of genistein was low, because of the first-pass metabolism. Thus, the reversing activity of genistein for P-gp in vivo was insufficient. We modified genistein chemically by methylation, but the water solubility became low. In studies with other natural products, some potent reversing agents for P-gp were found. By using them, further study is necessary to find potent but safer reversing agents.
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