Effect of hyperthermia on the activity of 1-[(4′-hydroxy-2′-butenoxy)methyl]-2-nitroimidazole, which is cytotoxic to hypoxic cells

Tetsuya Kusumoto, Yoshihiko Maehara, Yasunori Emi, Yoshihisa Sakaguchi, Hideo Baba, Masakazu Sakaguchi, Keizo Sugimachi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The effect on EMT6/KU cells of a newly synthesized hypoxic cell sensitizer, 1-[(4′-hydroxy-2′-butenoxy)methyl]-2-nitroimidazole (RK28), combined with heat was determined in vitro under conditions of hypoxia. As compared with aerobic conditions, hypoxia produced a 1.30-fold increase in the cytotoxicity of the drug for mouse mammary EMT6/KU cells induced by 1 h heat treatment at 43° C in medium with a normal pH. Hypoxia also reduced the surviving fraction of cells treated with both RK28 alone for 2 h and the same concentrations of RK28 and heat (43° C) in combination. Those enhancement ratios corresponded to a 20.3- and >345-fold increase, respectively. Moreover, concomitant treatment with RK28 and heat greatly inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia and in all experimental groups; there was a statistically significant difference in the time-response curves (P<0.05). As hypoxic cells in a solid tumor are resistant to various anticancer drugs, RK28 combined with hyperthermia deserves further study for possible clinical applications.

Original languageEnglish
Pages (from-to)455-458
Number of pages4
JournalCancer chemotherapy and pharmacology
Volume31
Issue number6
DOIs
Publication statusPublished - Nov 1 1993

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Effect of hyperthermia on the activity of 1-[(4′-hydroxy-2′-butenoxy)methyl]-2-nitroimidazole, which is cytotoxic to hypoxic cells'. Together they form a unique fingerprint.

  • Cite this