PMID- 10487422
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20220331
IS  - 1095-6670 (Print)
IS  - 1095-6670 (Linking)
VI  - 13
IP  - 6
DP  - 1999
TI  - The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in 
      human acute myeloid leukemia HL-60 cells via caspase-3 activation.
PG  - 338-47
AB  - Some widely used antidepressants such as imipramine, clomipramine, and citalopram 
      have been found to possess antineoplastic effects. In the present study, these 
      compounds were found to induce apoptotic cell death in human acute myeloid 
      leukemia HL-60 cells. Apoptosis induced by the antidepressants was identified by 
      electron microscopy and conventional agarose gel electrophoresis and was 
      quantitated by propodium iodide staining and the terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) via flow cytometry. Treatment 
      with apoptosis-inducing concentrations of the antidepressants (80 microM 
      imipramine, 35 microM clomipramine, or 220 microM citalopram) caused induction of 
      caspase-3/caspase-3-like activity, which was monitored by the cleavage of 
      poly(ADP-ribose) polymerase (PARP), the loss of the 32 kD caspase-3 (CPP32) 
      precursor, and the cleavage of the fluorescent CPP32-like substrate PhiPhiLux. 
      Pretreatment with a potent caspase inhibitor 
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (zVAD-fmk) inhibited 
      antidepressant-induced CPP32/CPP32-like activity and apoptosis. Furthermore, 
      activation of caspase induced by the antidepressants was preceded by the 
      hypergeneration of intracellular reactive oxygen species (ROS). These results 
      suggested that the antidepressants may induce apoptosis via a caspase-3-dependent 
      pathway, and induction of apoptosis by the antidepressants may provide a clue for 
      the mechanism of their antineoplastic effects.
FAU - Xia, Z
AU  - Xia Z
AD  - Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden. 
      xia@tuborg.biokemi.su.se
FAU - Bergstrand, A
AU  - Bergstrand A
FAU - DePierre, J W
AU  - DePierre JW
FAU - Nassberger, L
AU  - Nassberger L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - 0 (Antidepressive Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0DHU5B8D6V (Citalopram)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - NUV44L116D (Clomipramine)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Antidepressive Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspase 3
MH  - Caspases/*metabolism
MH  - Citalopram/pharmacology
MH  - Clomipramine/pharmacology
MH  - DNA Fragmentation/drug effects
MH  - Flow Cytometry
MH  - HL-60 Cells/*drug effects/enzymology/ultrastructure
MH  - Humans
MH  - Imipramine/pharmacology
MH  - In Situ Nick-End Labeling
MH  - Leukemia, Promyelocytic, Acute/pathology
MH  - Reactive Oxygen Species/metabolism
EDAT- 1999/09/16 09:00
MHDA- 2000/08/12 11:00
CRDT- 1999/09/16 09:00
PHST- 1999/09/16 09:00 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 1999/09/16 09:00 [entrez]
AID - 10.1002/(SICI)1099-0461(1999)13:6<338::AID-JBT8>3.0.CO;2-7 [pii]
AID - 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 
      10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.