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

Cellular resistance of cisplatin is related to variousfactors such as membrane transformations, changes incellular transport systems, andan increased efflux of cisplatin by the tumor cells. Deficiencies of one ormoretrace metals can affect normal physiological functions, leading to altered enzymaticactivities and areduction in immune responses. This in vitro investigation was undertaken tostudy and determine the differ-entialcytotoxicity of certain trace metals in humanovarian cancer cells that were sensitive and resistant tocisplatin. Standardcytotoxicity assays were performed using the neutral red assay. In general, thecisplatin-resistantcells exhibited an increased resistance to the externally supplied trace metals. For bothcell linesthe rank order of cytotoxicity from greatest to least with the non-essentialmetals was Cd >Bi , and forthe macrometals, Ca >K + >Mg . The transition metals and selenium exhibited a slight difference betweenthe two celllines with respect to the order of cytotoxicity. The cisplatin-sensitive cells had a rankorder ofV >Se >Cu >Zn >Fe , from greatest to least toxicity. The cisplatin-resistant cells had a rank orderof Cu >V >Se >Zn >Fe . Since trace metals have various functions in maintaining normal health,these results provide key baselinecytotoxicity data and show that, in general, cytotoxic resistance to thetrace metals testedfollowed a pattern similar to cellular cisplatin resistance.