PMID- 8645347 OWN - NLM STAT- MEDLINE DCOM- 19960715 LR - 20190623 IS - 0006-2952 (Print) IS - 0006-2952 (Linking) VI - 51 IP - 9 DP - 1996 May 3 TI - Differential effects of phorbol ester on apoptosis in HL-60 promyelocytic leukemia cells. PG - 1229-36 AB - 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. FAU - Zhu, W H AU - Zhu WH AD - Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong. FAU - Loh, T T AU - Loh TT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Enzyme Inhibitors) RN - 0 (Terpenes) RN - 37H9VM9WZL (Calcimycin) RN - 67526-95-8 (Thapsigargin) RN - 76455-48-6 (4-bromo-A-23187) RN - EC 2.7.11.13 (Protein Kinase C) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SY7Q814VUP (Calcium) SB - IM MH - Apoptosis/*drug effects MH - Calcimycin/analogs & derivatives/pharmacology MH - Calcium/metabolism MH - Down-Regulation MH - Enzyme Inhibitors/pharmacology MH - HL-60 Cells MH - Homeostasis/drug effects MH - Humans MH - Protein Kinase C/antagonists & inhibitors/metabolism MH - Terpenes/antagonists & inhibitors/pharmacology MH - Tetradecanoylphorbol Acetate/*pharmacology MH - Thapsigargin EDAT- 1996/05/03 00:00 MHDA- 1996/05/03 00:01 CRDT- 1996/05/03 00:00 PHST- 1996/05/03 00:00 [pubmed] PHST- 1996/05/03 00:01 [medline] PHST- 1996/05/03 00:00 [entrez] AID - 0006295296000962 [pii] AID - 10.1016/0006-2952(96)00096-2 [doi] PST - ppublish SO - Biochem Pharmacol. 1996 May 3;51(9):1229-36. doi: 10.1016/0006-2952(96)00096-2.