Influence of metabolic inhibitors on the intracellular accumulation and retention of adriamycin

Jun Ichi Asaumi, Shoji Kawasaki, Masahiro Kuroda, Yoshihiro Takeda, Kanji Kishi, Yoshio Hiraki

Research output: Contribution to journalArticle

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Abstract

We observed modulation of the intracellular accumulation and retention of adriamycin (ADR) by metabolic inhibitors in Ehrlich ascites tumor cells (wild type EAT cells) and their ADR-resistant EAT strain. In the wild type EAT cells, ADR accumulation was increased by 0.2 mM of 2,4-dinitrophenol (2,4-DNP), 1 mM of sodium azide (NaN3) or 1 mM of potassium cyanide (KCN), which were the metabolic inhibitors, and its efflux was inhibited by the metabolic inhibitors several fold. These results indicate that in wild type EAT cells, one of the mechanisms which increase the intracellular accumulation of ADR involve inhibition of efflux, which may be inhibited by these metabolic inhibitors. In ADR-resistant EAT strain, 2,4-DNP or KCN increased the ADR accumulation, but NaN3 did not affect it. Further, ADR efflux in the ADR-resistant cells after incubation with the metabolic inhibitors were similar to that found in the control. Thise indicates that in the ADR-resistant cells, NaN3 does not affect ADR accumulation by KCN and 2,4-DNP was considered to be due to the influx rather than efflux. In addition, 2,4-DNP, NaN3 or KCN inhibited ADR efflux in the wild type EAT cells but not in the ADR-resistant EAT strain. Thise suggests that there is an efflux mechanism in the ADR-resistant EAT strain that involves an energy system that differs from the energy system in wild type EAT cells or does not depend on energy produced by the metabolic inhibitors.

Original languageEnglish
Pages (from-to)615-618
Number of pages4
JournalAnticancer research
Volume19
Issue number1 A
Publication statusPublished - 1999

Keywords

  • 2,4-Dinitrophenol
  • Adriamycin
  • Potassium cyanide
  • Sodium azide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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