Induced Anticancer Drug Resistance in Cell Culture

Metal-Induced Anticancer Drug Resistance in Cell Culture 

Bakka et al. (1981) were among the first to suggest a role for metals in resistance to electrophilic anticancer drugs when they noted mammalian cells made chronically resistant to Cd were cross-resistant to the toxic effects of cisplatin. In subsequent studies they found the sensitivity of Cd-resistant cells was reduced by 1.5- to 3-fold not only to cisplatin but also to chlorambucil and prednimustine (Endresen et al. 1983 Endresen and Rugstad 1987). Andrews et al. (1987) and Kelley et al. (1988) confirmed that Cd-resistant human tumor cells were cross-resistant to cisplatin. Moreover, Andrews et al. (1987) demonstrated that Cd-resistant cells did not have a decreased uptake of radiolabeled cisplatin. Webber et al. (1988) examined the sensitivity of Cd-resistant human DU-145 prostate cells to the anthra-cycline doxorubicin. A very modest (1.5-fold) resistance to doxorubicin was observed but the specificity of this resistance with respect to other antineo-plastic agents was not determined. 

Chronic exposure of mammalian cells to Cd generally increases the synthesis of the metal-binding protein metallothionein often this is associated with an increase in metallothionein gene copy number. In all of the above-mentioned studies increases in metallothionein were noted. 

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C. Metal-Induced Anticancer Drug Resistance in Cell Culture... 

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