Copper(II) protects yeast against the toxicity of cisplatin independently of the induction of metallothionein and the inhibition of platinum uptake

Kazuaki Ohashi, Kazuki Kajiya, Sachiko Inaba, Tatsuya Hasegawa, Yoshiyuki Seko, Takemitsu Furuchi, Akira Naganuma

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

We have made the unexpected discovery that copper sulfate protects Saccharomyces cerevisiae from the toxic effects of cisplatin. Addition of copper to the culture medium of yeast cells at concentrations above 0.1μM significantly reduced the toxicity of cisplatin. Since a high-affinity copper transporter, Ctr1, has been reported to play a major role in the uptake of cisplatin, we examined the effects of copper on the cellular uptake of cisplatin. We found that the cellular concentration of platinum was not significantly affected by treatment of cells with 1μM copper. It is known that mammalian metallothionein is induced by copper and is involved in acquired resistance to cisplatin. Copper significantly increased the level of mRNA for yeast metallothionein at a concentration that has effectively reduced the toxicity of cisplatin. However, the toxicity of cisplatin in cells with a disrupted gene for ACE1, a factor that regulates transcription of the yeast gene for metallothionein, was also significantly reduced by treatment with copper. These results suggest that copper protects yeast cells from cisplatin toxicity independently of induction of the synthesis of metallothionein and of the inhibition of platinum uptake. Since copper is one of the trace elements that are essential for cell function and since a relatively low concentration of copper (0.1μM) significantly reduced cisplatin toxicity, it is possible that copper might play an important role in the expression of cisplatin toxicity.

Original languageEnglish
Pages (from-to)148-152
Number of pages5
JournalBiochemical and biophysical research communications
Volume310
Issue number1
DOIs
Publication statusPublished - 2003 Oct 10

Keywords

  • Cisplatin
  • Copper
  • Metallothionein
  • Resistance
  • Yeast

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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