Effect of copper and role of the copper transporters ATP7A and CTR1 in intracellular accumulation of cisplatin

Shinobu Matsumoto, Toshiko Tanaka, Hideo Kurokawa, Koji Matsuno, Yutaka Hayashida, Tetsu Takahashi

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20 Citations (Scopus)


An investigation was carried out as to whether copper affected the intracellular accumulation of cisplatin (cis-diamminedichloroplatinum(II); CDDP) and whether changes in the expression of ATP7A and CTR1 were related to acquired resistance using CDDP-sensitive (KB) and -resistant (KBR/0.8, KBR/1.2) cells. Intracellular platinum accumulation and platinum-DNA adducts were significantly lower in the CDDP-resistant sublines compared with KB cells. Treatment with 750 μM CuSO4 increased the amount of intracellular platinum 1.8-, 3.2-, and 3.9-fold in KB, KBR/0.8, and KBR/1.2 cells respectively, and increased the platinum-DNA adducts by 1.9-fold in KB cells and by 3.2-fold in KBR/1.2 cells. The level of ATP7A was greatly reduced and CTR1 expression slightly decreased in KBR/1.2 cells compared with KB cells. ATP7A expression was markedly increased by exposure to CDDP with or without copper in KB cells but not in KBR/1.2 cells. CDDP and copper did not increase the level of CTR1 in KB or KBR/1.2 cells. These results indicate that a high concentration of copper causes a significant increase in the cellular accumulation of CDDP and binding of platinum to DNA independently of CTR1 expression in KB cells and CDDP-resistant sublines thereof and that the acquisition of CDDP resistance is associated with a greatly reduced level of ATP7A and a marginally lower expression of CTR1.

Original languageEnglish
Pages (from-to)2209-2216
Number of pages8
JournalAnticancer research
Issue number4 B
Publication statusPublished - 2007 Jul
Externally publishedYes


  • ATP7A
  • CTR1
  • Cisplatin
  • Cisplatin resistance
  • Copper
  • Human epidermoid cancer KB cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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