EFFECT OF 12-DEOXYPHORBOL 13-PHENYLACETATE ON DAUNORUBICIN RESISTANCE AND CALCIUM-INDEPENDENT PROTEIN-KINASE-C ISOZYMES IN DRUG-SENSITIVE MURINE LEUKEMIA P388 CELLS

Abstract

Because of a suggested role of protein kinase C (PKC) in multidrug resistance (MDR) and recent. demonstration of molecular and biochemical heterogeneity of PKC, we examined the effect of 12-deoxyphorbol 13-phenylacetate (dPP) on intracellular accumulation and drug sensitivity of daunorubicin (DNR) in drug sensitive P388 murine leukemia cell line. In addition, effect of dPP on Ca++-independent PKC (delta, epsilon and zeta) isozymes was examined with Western blot, using laser densitometry. dPP induced significant resistance to DNR in P388 cells, however had no significant effect on DNR accumulation. In addition, dPP increased the levels of plasma membrane associated PKCdelta and epsilon isozymes in P388 cells and but had no effect on plasma membrane-associated PKCzeta isozyme. This study demonstrates a role of Ca++-independent PKCdelta and epsilon isozymes in drug resistance.