NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy

Int J Oncol. 2000 Feb;16(2):295-303. doi: 10.3892/ijo.16.2.295.


We attempted to determine a target of chemotherapy specific to glioblastoma cells to ensure a favorable response to anticancer drugs, through comparison in biologic nature related to drug resistance with other types of cancer cells. Using 13 human cancer cell lines including 3 glioblastoma lines, gene expression analysis and biochemical quantitative assay were performed for a total of 12 properties, which have been linked to drug action. Although most of genes related to drug resistance, such as MDR1, MRP, MGMT and GSTpi, were overexpressed in T98G, U-373MG, and U-251MG glioblastoma cells, Topo I (topoisomerase I) expression was relatively low and alpha- and beta-TUB (tubulin) expression was comparable to other types of 10 cell lines. The glioblastoma cell lines also showed an increased expression of NADPH/quinone oxidoreductase gene (NQO1), but the respective enzyme NQO activated MMC. Among the drugs targeting such properties, MMC was more active than Topo I inhibitors and docetaxel (TXT) due to the lack of other sensitivity (resistance) determinants. Differing from MMC, MGMT was shown to participate in the resistance of Topo I inhibitors (CPT-11, SN-38 and DX-8951f), while GSTpi and MDR1 were involved in docetaxel (TXT) resistance. MMC was also more active than ACNU and CDDP in the three glioblastoma cells. NQO may be a priority target of glioblastoma chemotherapy suitable for biochemical nature of the cells, and expression analysis of NQO1, alpha-TUB, beta-TUB, MGMT, MDR1 and GSTpi may help to seek a truly active drug against glioblastomas.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • DNA Topoisomerases, Type I / drug effects
  • DNA Topoisomerases, Type I / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme Inhibitors / pharmacology
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glutathione / drug effects
  • Glutathione / metabolism
  • Glutathione Transferase / drug effects
  • Glutathione Transferase / metabolism
  • Humans
  • Mitomycin / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / drug effects
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / metabolism*
  • Tubulin / drug effects
  • Tubulin / metabolism


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Tubulin
  • Mitomycin
  • NAD(P)H Dehydrogenase (Quinone)
  • Glutathione Transferase
  • DNA Topoisomerases, Type I
  • Glutathione