[Multidrug-resistance by induction of inactivation for anti-cancer drugs]

Nihon Rinsho. 1997 May;55(5):1044-9.
[Article in Japanese]

Abstract

There are several major groups of multidrug resistance mechanisms. 1) The multidrug resistant phenotype. 2) Glutathione S-transferences (GST) and detoxification mechanisms. 3) Topoisomerase I and II. 4) DNA repair. 5) Drug activation by cytochrome P450 (P450). In this article the biochemical functions of GST and P450 are described to show how individual enzymes contribute to resistance to carcinogens and anti-tumor drugs. Cancer cell lines indicated resistant to anti-cancer drugs, such as mitomycin C, doxorubicin, tamoxifen, cyclophosphamide and their derivatives, by a high activity of GST and a low activity of P450 in general. However, the mechanism of change of these enzyme activities is complicated and different in each drug. We show the study on the mechanism of multidrug resistance using cancer cell lines.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Biotransformation
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochrome P-450 Enzyme System / physiology
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Glutathione Transferase / metabolism
  • Glutathione Transferase / physiology
  • Humans
  • Neoplasms / enzymology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cytochrome P-450 Enzyme System
  • Glutathione Transferase