がん耐性因子を標的とした抗がん剤の耐性克服 : 温故知新 : グルタチオンおよびグリオキサラーゼIを標的とした耐性克服研究 Reversal of Anticancer Drug Resistance Targetting Intracellular Glutathione and Glyoxalase I

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Emergence of resistance to anticancer agents is a serious problem in cancer chemotherapy. We studied on the suppression of anticancer drug resistance targetting the overexpressed glutathione (GSH) in apoptosis-resistant tumor cells and glyoxalase I (GloI). GloI is an enzyme that plays a role in the detoxification of methylglyoxal utilizing GSH as an essential cofactor. Inhibitors of GloI have been found to exhibit antiproliferative effects on cancerous cells. Hence, potent GloI inhibitors could proved to be valuable anticancer agents. COTC, an inhibitor of GloI isolated from the culture broth of <i>Streptomyces griseosporeus</i>, had no effect on GloI in the absence of GSH. We reexamined the reaction of COTC with GSH and found that STCG was the real inhibitor of GloI. AsPC-1 cells show the drug-resistance against anticancer drugs because of the over-expression of GSH. When AsPC-1 cells were treated with several anticancer drugs in the presence of COTC, the sensitivity of AsPC-1 cells to CDDP and melphalan was significantly increased. Next, we synthesized ACDC containing adriamycin as an anticancer drug in a molecule. Treatment of ACDC with GSH released adriamycin and SDCG. Evaluation of ACDC against adriamycin-resistant L1210 cells showed significant increase of sensitivity and the prolonged life span of mice bearing P388 leukemia was observed.

収録刊行物

  • 有機合成化学協会誌

    有機合成化学協会誌 70(3), 240-249, 2012-03-01

    社団法人 有機合成化学協会

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各種コード

  • NII論文ID(NAID)
    10030481690
  • NII書誌ID(NCID)
    AN0024521X
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    00379980
  • NDL 記事登録ID
    023581353
  • NDL 請求記号
    Z17-256
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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