PMID- 14511359
OWN - NLM
STAT- MEDLINE
DCOM- 20031204
LR  - 20190827
IS  - 0014-2972 (Print)
IS  - 0014-2972 (Linking)
VI  - 33
IP  - 10
DP  - 2003 Oct
TI  - Activation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 
      human oral cancer cells.
PG  - 875-82
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic 
      acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, 
      the signalling molecules involved remain unclear. The aim of this study was to 
      investigate the possible existence of a putative p53-dependent pathway underlying 
      the ASA-induced apoptosis in OC2 cells, a human oral cancer cell line. MATERIALS 
      AND METHODS: The methyl tetrazolium (MTT) assay was employed to quantify 
      differences in cell viability. DNA ladder formation on agarose electrophoresis 
      was used as apoptosis assay. The expression levels of several master regulatory 
      molecules controlling various signal pathways were monitored using the 
      immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA 
      on cell cycle. Patterns of changes in expression were scanned and analyzed using 
      the NIH image 1.56 software (NIH, Bethesda, MD, USA). All the data were analyzed 
      by ANOVA. RESULTS: Acetylsalicylic acid reduced cell viability and presence of 
      internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at 
      serine 15, accumulation of p53 and increased the expression of its downstream 
      target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase-2 was 
      suppressed. Disruption of p53-murine double minute-2 (MDM2) complex formation 
      resulted in increasing the expression of MDM2 60-kDa cleavage fragment. Inhibited 
      the activation of p42/p44 mitogen-activated protein kinase (MAPK) by PD98059, a 
      specific inhibitor of extracellular regulatory kinase (ERK), significantly 
      decreased cell viability and enhanced the expression of p53 induced by ASA. The 
      result of the cell-cycle analysis showed that ASA and PD98059 induced the cell 
      cycle arrested at the G0/G1 phase and resulted in apoptosis. CONCLUSION: 
      Nonsteroidal anti-inflammatory drug-inhibited cyclooxygenase is not the only or 
      even the most important mechanism of inhibition. Our study presents evidences 
      that activation of p53 signalling involved in apoptosis induced by ASA. 
      Furthermore, the apoptotic effect was enhanced by blocking the activation of 
      p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role 
      for p42/p44 MAPK.
FAU - Ho, C-C
AU  - Ho CC
AD  - Department of Dentistry, Chung Shan Medical University Hospital, Taichung, 
      Taiwan.
FAU - Yang, X W
AU  - Yang XW
FAU - Lee, T-L
AU  - Lee TL
FAU - Liao, P-H
AU  - Liao PH
FAU - Yang, S-H
AU  - Yang SH
FAU - Tsai, C-H
AU  - Tsai CH
FAU - Chou, M-Y
AU  - Chou MY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EUY85H477I (thiazolyl blue)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Apoptosis/drug effects
MH  - Aspirin/*pharmacology
MH  - Cell Cycle/drug effects
MH  - Cell Division/drug effects
MH  - Cyclooxygenase 2
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Isoenzymes/antagonists & inhibitors
MH  - Membrane Proteins
MH  - Mitogen-Activated Protein Kinases/physiology
MH  - Mouth Neoplasms/*metabolism/pathology
MH  - Neoplasm Proteins/*metabolism
MH  - *Nuclear Proteins
MH  - Prostaglandin-Endoperoxide Synthases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Signal Transduction/drug effects
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Up-Regulation/drug effects
EDAT- 2003/09/27 05:00
MHDA- 2003/12/05 05:00
CRDT- 2003/09/27 05:00
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2003/12/05 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
AID - 1240 [pii]
AID - 10.1046/j.1365-2362.2003.01240.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2003 Oct;33(10):875-82. doi: 10.1046/j.1365-2362.2003.01240.x.