PMID- 15978937
OWN - NLM
STAT- MEDLINE
DCOM- 20050812
LR  - 20180815
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 29
IP  - 8
DP  - 2005 Aug
TI  - Signal transduction of phorbol 12-myristate 13-acetate (PMA)-induced growth 
      inhibition of human monocytic leukemia THP-1 cells is reactive oxygen dependent.
PG  - 863-79
AB  - Human monocytic THP-1 cells can be induced to differentiate to macrophages when 
      treated with phorbol 12-myristate 13-acetate (PMA). It is understood that before 
      initiating cell differentiation, PMA treatment must first induce an inhibition of 
      cell growth. Since the initial biochemical and molecular events that are 
      associated with this growth inhibition have not been characterized, the present 
      study was carried out to elucidate the molecular mechanisms associated with the 
      PMA-induced growth arrest of THP-1 cells. Our results indicate that PMA inhibits 
      THP-1 cells at G1-phase of the cell cycle, via a complex mechanism associated 
      with the modulation of the expression of several cell cycle regulators, initiated 
      by the cellular generation of reactive oxygen species (ROS). Both p21WAF1/CIP1 
      mRNA and protein were upregulated 24 h post PMA treatment as demonstrated by 
      ribonuclease protection assay and Western blotting, respectively. Because these 
      cells lack functional p53, this effect was independent of p53 activity. 
      Electrophoretic mobility shift assay showed that the PMA-induced activation of 
      the p21WAF1/CIP1 promoter was driven by the specific protein 1 (Sp1) 
      transcription factor through Sp1-binding sites. Additionally, our study 
      demonstrates that PMA-induces the upregulation of p21 through a protein kinase C 
      (PKC)-mediated ROS-dependent signaling mechanism involving MAP kinase activation.
FAU - Traore, Kassim
AU  - Traore K
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, Howard 
      University, Washington, DC, USA. ktraore@jhsph.edu
FAU - Trush, Michael A
AU  - Trush MA
FAU - George, Matthew Jr
AU  - George M Jr
FAU - Spannhake, Ernst Wm
AU  - Spannhake EW
FAU - Anderson, Winston
AU  - Anderson W
FAU - Asseffa, Amha
AU  - Asseffa A
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050224
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Antioxidants)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Flavonoids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Retinoblastoma Protein)
RN  - 56937-68-9 (phorbolol myristate acetate)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Antioxidants/pharmacology
MH  - CDC2-CDC28 Kinases/antagonists & inhibitors
MH  - Cell Cycle/drug effects
MH  - Cell Cycle Proteins/drug effects/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Flavonoids/pharmacology
MH  - G1 Phase/drug effects
MH  - Gene Expression Regulation, Leukemic/*drug effects
MH  - Humans
MH  - Monocytes/*drug effects
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - RNA, Messenger/drug effects
MH  - Reactive Oxygen Species/*metabolism
MH  - Retinoblastoma Protein/drug effects/metabolism
MH  - S Phase/drug effects
MH  - Signal Transduction/*drug effects
MH  - Tetradecanoylphorbol Acetate/*analogs & derivatives/antagonists & 
      inhibitors/*pharmacology
MH  - Time Factors
EDAT- 2005/06/28 09:00
MHDA- 2005/08/13 09:00
CRDT- 2005/06/28 09:00
PHST- 2004/07/19 00:00 [received]
PHST- 2004/12/19 00:00 [accepted]
PHST- 2005/06/28 09:00 [pubmed]
PHST- 2005/08/13 09:00 [medline]
PHST- 2005/06/28 09:00 [entrez]
AID - S0145-2126(05)00045-7 [pii]
AID - 10.1016/j.leukres.2004.12.011 [doi]
PST - ppublish
SO  - Leuk Res. 2005 Aug;29(8):863-79. doi: 10.1016/j.leukres.2004.12.011. Epub 2005 
      Feb 24.