Differential effects of phorbol ester on apoptosis in HL-60 promyelocytic leukemia cells.
The role of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) in apoptosis of HL-60 cells was investigated. PMA inhibited DNA fragmentation induced by thapsigargin (TG) and 4-bromo-calcium ionophore (Br-A23187). The inhibitory effect of PMA was concentration-related and was abolished by a specific PKC inhibitor, bisindolylmaleimide (GF109203X. In addition TG-induced apoptosis was decreased in cells in which PKC activity was down-regulated by long-term pretreatment with PMA. These results indicate that PKC activation by PMA inhibits HL-60 cell apoptosis induced by TG and Br-A23187, and that this inhibition is not influenced by the down-regulation of PKC. However, PMA did not inhibit DNA fragmentation induced by 1-beta-D-arabinofuranosylcytosine (Ara-C) and cycloheximide. PMA suppressed TG- or Br-A23187. Our results indicate that PKC participates in the regulation of apoptosis only by some pathways. Down-regulation of PKC is not responsible for the diverse effects of PKC activators on apoptosis. The effect of a PKC modulator on apoptosis is dependent upon interaction with individual apoptotic stimulus.
Zhu
W H
WH
Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Loh
T T
TT
D017209:Apoptosis / Q000187:drug effects*; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013729:Terpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019284:Thapsigargin
D004791:Enzyme Inhibitors; D013729:Terpenes; D000001:Calcimycin; D019284:Thapsigargin; C033170:4-bromo-A-23187; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium