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, Me2SO 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.
Heesbeen
E C
EC
Department of Hematology, University Hospital Utrecht, The Netherlands.
Verdonck
L F
LF
Staal
G E
GE
Rijksen
G
G
D000470:Alkaloids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D013936:Thymidine / Q000378:metabolism
D000470:Alkaloids; D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; C026659:edelfosine; D011493:Protein Kinase C; D019311:Staurosporine; D013936:Thymidine