PMID- 23799549
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20130705
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 8
IP  - 2
DP  - 2013 Aug
TI  - The effect of MAPK inhibitors and ROS modulators on cell growth and death of 
      H(2)O(2)-treated HeLa cells.
PG  - 557-64
LID - 10.3892/mmr.2013.1551 [doi]
AB  - Reactive oxygen species (ROS) influence the signaling of mitogen‑activated 
      protein kinases (MAPKs) involved in cell survival and death. In the present 
      study, the toxicological effect of hydrogen peroxide (H2O2) on HeLa cervical 
      cancer cells was evaluated following treatment with MAPK inhibitors [MAP kinase 
      or ERK kinase (MEK), c‑Jun N‑terminal kinase (JNK) or p38], N‑acetyl cysteine 
      (NAC) and propyl gallate (PG) (well‑known antioxidants), or L‑buthionine 
      sulfoximine [BSO; an inhibitor of glutathione (GSH) synthesis]. Treatment with 
      100 microM H2O2 inhibited the growth of HeLa cells and induced cell death, which was 
      accompanied by loss of the mitochondrial membrane potential (MMP; DeltaPsim). H2O2 did 
      not induce any specific phase arrests of the cell cycle. ROS levels increased, 
      while GSH levels decreased in H2O2‑treated HeLa cells after 1 and 24 h of 
      treatment. The MAPK inhibitors enhanced H2O2‑induced HeLa cell death, while only 
      p38 inhibitor increased ROS levels. Both NAC and PG attenuated H2O2‑induced HeLa 
      cell growth inhibition and death together with the suppression of ROS levels. BSO 
      increased ROS levels in H2O2‑treated HeLa cells without increasing cell death. 
      The levels of MMP (DeltaPsim) loss and GSH depletion were not closely associated with 
      the levels of apoptosis in HeLa cells treated with the MAPK inhibitors, NAC, PG 
      or BSO, in the presence of H2O2. In conclusion, H2O2 induced HeLa cell growth 
      inhibition and death. MAPK inhibitors generally enhanced H2O2‑induced HeLa cell 
      death. In particular, p38 inhibitor increased ROS levels in H2O2‑treated HeLa 
      cells, while NAC and PG attenuated H2O2‑induced HeLa cell death by suppressing 
      ROS levels.
FAU - Park, Woo Hyun
AU  - Park WH
AD  - Department of Physiology, Medical School, Research Institute for Endocrine 
      Sciences, Chonbuk National University, JeonJu 561‑180, Republic of Korea. 
      parkwh71@chonbuk.ac.kr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130625
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antioxidants)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Cell Death/drug effects
MH  - Cell Proliferation/drug effects
MH  - Glutathione/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Reactive Oxygen Species/*metabolism
EDAT- 2013/06/27 06:00
MHDA- 2014/02/14 06:00
CRDT- 2013/06/27 06:00
PHST- 2013/02/01 00:00 [received]
PHST- 2013/06/10 00:00 [accepted]
PHST- 2013/06/27 06:00 [entrez]
PHST- 2013/06/27 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
AID - 10.3892/mmr.2013.1551 [doi]
PST - ppublish
SO  - Mol Med Rep. 2013 Aug;8(2):557-64. doi: 10.3892/mmr.2013.1551. Epub 2013 Jun 25.