PROTEIN-KINASE-C IS NOT INVOLVED IN THE CYTOTOXIC ACTION OF 1-OCTADECYL-2-O-METHYL-SN-GLYCEROL-3-PHOSPHOCHOLINE IN HL-60 AND K562 CELLS

We studied the effects of the alkyllysophospholipid 1-octadecyl-2-O-methyl-sn-glycerol-3-phosphocholine (ET-18-OCH3) on membrane associated protein kinase C (PK-C) activity in ET-18-OCH3 sensitive HL-60 cells and in two resistant cell types, Me(2)SO differentiated HL-60 cells and K562 cells. HL-60 cells expressed a lower PK-C activity level compared with both resistant cell types. However, membrane-bound PK-C activity in the sensitive HL-60 cells was approximately 3-fold increased in the presence of ET-18-OCH3, whereas in differentiated HL-60 cells and K562 cells PK-C was not influenced by ET-18-OCH3. The increase in PK-C activity in HL-60 cells was not due to translocation of cytosolic PK-C or synthesis de novo. The effect of ET-18-OCH3 on kinetic parameters of PK-C in all three cell types was investigated in order to elucidate the nature of the ET-18-OCH3 effects on PK-C activity in both sensitive and resistant cell types. A functional relationship between PK-C level and effect of ET-18-OCH3 on PK-C activity in the different cell types could not be found. Moreover, cells depleted of PK-C activity showed similar sensitivity or resistance to ET-18-OCH3 as cells expressing PK-C activity. These results suggest that a role of PK-C in the cytotoxic action of ET-18-OCH3 is very unlikely.