[Multidrug-resistance by induction of inactivation for anti-cancer drugs].
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.
Ishii
I
I
Faculty of Pharmaceutical Sciences, Chiba University.
Kitada
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000502:physiology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005982:Glutathione Transferase / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000201:enzymology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase