Abstract
A role of protein kinase C (PKC) has been suggested in multidrug resistance (MDR). Because of the molecular and biochemical heterogeneity of PKC, we examined a role of PKC beta isozyme in drug sensitive murine leukemia P388 cell line. Drug sensitive P388 and MDR P388/ADR cells were treated with various concentrations of 12-deoxyphorbol-13-O-phenylacetate 20 acetate (DPPA, an agonist of PKC beta I isozyme) and examined for its effect on daunorubicin (DNR) accumulation and sensitivity to DNR. dPPA increased DNR resistance and decreased DNR accumulation in P388 cells but had no effect in P388/ADR cells. The reduced dPPA-induced DNR accumulation was due to decreased uptake without any effect on DNR efflux. Furthermore, treatment of P388 cells with dPPA was associated with translocation of PKC beta isozyme from cytosol to plasma membrane. These data suggest that PKC beta I isozyme plays a role in acquired drug resistance.
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