Differential cytotoxicity of trace metals in cisplatin-sensitive and -resistant human ovarian cancer cells

Biometals. 1998 Sep;11(3):259-63. doi: 10.1023/a:1009285007366.


Cellular resistance of cisplatin is related to various factors such as membrane transformations, changes in cellular transport systems, and an increased efflux of cisplatin by the tumor cells. Deficiencies of one or more trace metals can affect normal physiological functions, leading to altered enzymatic activities and a reduction in immune responses. This in vitro investigation was undertaken to study and determine the differential cytotoxicity of certain trace metals in human ovarian cancer cells that were sensitive and resistant to cisplatin. Standard cytotoxicity assays were performed using the neutral red assay. In general, the cisplatin-resistant cells exhibited an increased resistance to the externally supplied trace metals. For both cell lines the rank order of cytotoxicity from greatest to least with the non-essential metals was Cd2+ > Bi3+, and for the macrometals, Ca2+ > K+ > Mg2+. The transition metals and selenium exhibited a slight difference between the two cell lines with respect to the order of cytotoxicity. The cisplatin-sensitive cells had a rank order of V5+ > Se6+ > Cu2+ > Zn2+ > Fe3+, from greatest to least toxicity. The cisplatin-resistant cells had a rank order of Cu2+ > V5+ > Se6+ > Zn2+ > Fe3+. Since trace metals have various functions in maintaining normal health, these results provide key baseline cytotoxicity data and show that, in general, cytotoxic resistance to the trace metals tested followed a pattern similar to cellular cisplatin resistance.

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity*
  • Cisplatin / adverse effects
  • Cisplatin / chemistry
  • Cisplatin / therapeutic use
  • Cisplatin / toxicity*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Metals / toxicity*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Metals
  • Cisplatin