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Article

The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells

  • Authors:
    • Woo Hyun Park
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, JeonJu 561‑180, Republic of Korea
  • Pages: 557-564
    |
    Published online on: June 25, 2013
       https://doi.org/10.3892/mmr.2013.1551
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Abstract

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 µM H2O2 inhibited the growth of HeLa cells and induced cell death, which was accompanied by loss of the mitochondrial membrane potential (MMP; ΔΨm). 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 (ΔΨm) 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.
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1 

Zelko IN, Mariani TJ and Folz RJ: Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 33:337–349. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Wilcox CS: Reactive oxygen species: roles in blood pressure and kidney function. Curr Hypertens Rep. 4:160–166. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Genestra M: Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 19:1807–1819. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Blenis J: Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci USA. 90:5889–5892. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Kusuhara M, Takahashi E, Peterson TE, Abe J, Ishida M, Han J, Ulevitch R and Berk BC: p38 Kinase is a negative regulator of angiotensin II signal transduction in vascular smooth muscle cells: effects on Na+/H+ exchange and ERK1/2. Circ Res. 83:824–831. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Hsin YH, Chen CF, Huang S, Shih TS, Lai PS and Chueh PJ: The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett. 179:130–139. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Mao X, Yu CR, Li WH and Li WX: Induction of apoptosis by shikonin through a ROS/JNK-mediated process in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells. Cell Res. 18:879–888. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Han YH, Moon HJ, You BR, Kim SZ, Kim SH and Park WH: JNK and p38 inhibitors increase and decrease apoptosis, respectively, in pyrogallol-treated calf pulmonary arterial endothelial cells. Int J Mol Med. 24:717–722. 2009.PubMed/NCBI

9 

Lee YJ, Kang IJ, Bünger R and Kang YH: Enhanced survival effect of pyruvate correlates MAPK and NF-kappaB activation in hydrogen peroxide-treated human endothelial cells. J Appl Physiol. 96:792–801. 2004.PubMed/NCBI

10 

Guyton KZ, Liu Y, Gorospe M, Xu Q and Holbrook NJ: Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem. 271:4138–4142. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Henson ES and Gibson SB: Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: implications for cancer therapy. Cell Signal. 18:2089–2097. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Rhee SG, Kang SW, Jeong W, Chang TS, Yang KS and Woo HA: Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. Curr Opin Cell Biol. 17:183–189. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Vilhardt F and van Deurs B: The phagocyte NADPH oxidase depends on cholesterol-enriched membrane microdomains for assembly. EMBO J. 23:739–748. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Han YH and Park WH: The effects of N-acetyl cysteine, buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to cell growth, reactive oxygen species and glutathione. Oncol Rep. 22:385–391. 2009.

15 

Han YH, Moon HJ, You BR, Kim SZ, Kim SH and Park WH: Effects of carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone on the growth inhibition in human pulmonary adenocarcinoma Calu-6 cells. Toxicology. 265:101–107. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Han YH, Kim SZ, Kim SH and Park WH: Pyrogallol inhibits the growth of human lung cancer Calu-6 cells via arresting the cell cycle arrest. Toxicol In Vitro. 22:1605–1609. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Han YH, Moon HJ, You BR and Park WH: The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH. Oncol Rep. 22:215–221. 2009.PubMed/NCBI

18 

Han YH, Kim SH, Kim SZ and Park WH: Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2•− generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells. Lung Cancer. 63:201–209. 2009.

19 

Han YH and Park WH: Propyl gallate inhibits the growth of HeLa cells via regulating intracellular GSH level. Food Chem Toxicol. 47:2531–2538. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Han YH, Kim SZ, Kim SH and Park WH: Intracellular GSH level is a factor in As4.1 juxtaglomerular cell death by arsenic trioxide. J Cell Biochem. 104:995–1009. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP and Wang X: Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 275:1129–1132. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Singh M, Sharma H and Singh N: Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway. Mitochondrion. 7:367–373. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Yamagishi N, Saito Y and Hatayama T: Mammalian 105 kDa heat shock family proteins suppress hydrogen peroxide-induced apoptosis through a p38 MAPK-dependent mitochondrial pathway in HeLa cells. FEBS J. 275:4558–4570. 2008. View Article : Google Scholar

24 

Reddan JR, Giblin FJ, Sevilla M, Padgaonkar V, Dziedzic DC, Leverenz VR, Misra IC, Chang JS and Pena JT: Propyl gallate is a superoxide dismutase mimic and protects cultured lens epithelial cells from H2O2 insult. Exp Eye Res. 76:49–59. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Wu TW, Fung KP, Zeng LH, Wu J and Nakamura H: Propyl gallate as a hepatoprotector in vitro and in vivo. Biochem Pharmacol. 48:419–422. 1994. View Article : Google Scholar : PubMed/NCBI

26 

Kobayashi H, Oikawa S, Hirakawa K and Kawanishi S: Metal-mediated oxidative damage to cellular and isolated DNA by gallic acid, a metabolite of antioxidant propyl gallate. Mutat Res. 558:111–120. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Kawanishi S, Oikawa S and Murata M: Evaluation for safety of antioxidant chemopreventive agents. Antioxid Redox Signal. 7:1728–1739. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Han YH, Moon HJ, You BR, Yang YM, Kim SZ, Kim SH and Park WH: Propyl gallate inhibits the growth of endothelial cells, especially calf pulmonary arterial endothelial cells via caspase-independent apoptosis. Int J Mol Med. 25:937–944. 2010.PubMed/NCBI

29 

Jacobi H, Eicke B and Witte I: DNA strand break induction and enhanced cytotoxicity of propyl gallate in the presence of copper(II). Free Radic Biol Med. 24:972–978. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Han YH, Kim SZ, Kim SH and Park WH: Enhancement of arsenic trioxide-induced apoptosis in HeLa cells by diethyldithiocarbamate or buthionine sulfoximine. Int J Oncol. 33:205–213. 2008.PubMed/NCBI

31 

Han YH, Kim SZ, Kim SH and Park WH: Suppression of arsenic trioxide-induced apoptosis in HeLa cells by N-acetylcysteine. Mol Cells. 26:18–25. 2008.PubMed/NCBI

32 

Estrela JM, Ortega A and Obrador E: Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci. 43:143–181. 2006. View Article : Google Scholar

33 

Han YH, Kim SZ, Kim SH and Park WH: Induction of apoptosis in arsenic trioxide-treated lung cancer A549 cells by buthionine sulfoximine. Mol Cells. 26:158–164. 2008.PubMed/NCBI

34 

Lewis-Wambi JS, Kim HR, Wambi C, Patel R, Pyle JR, Klein-Szanto AJ and Jordan VC: Buthionine sulfoximine sensitizes antihormone-resistant human breast cancer cells to estrogen-induced apoptosis. Breast Cancer Res. 10:R1042008. View Article : Google Scholar

35 

Ramos AM and Aller P: Quercetin decreases intracellular GSH content and potentiates the apoptotic action of the antileukemic drug arsenic trioxide in human leukemia cell lines. Biochem Pharmacol. 75:1912–1923. 2008. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Park WH: The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells. Mol Med Rep 8: 557-564, 2013.
APA
Park, W.H. (2013). The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells. Molecular Medicine Reports, 8, 557-564. https://doi.org/10.3892/mmr.2013.1551
MLA
Park, W. H."The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells". Molecular Medicine Reports 8.2 (2013): 557-564.
Chicago
Park, W. H."The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells". Molecular Medicine Reports 8, no. 2 (2013): 557-564. https://doi.org/10.3892/mmr.2013.1551
Copy and paste a formatted citation
x
Spandidos Publications style
Park WH: The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells. Mol Med Rep 8: 557-564, 2013.
APA
Park, W.H. (2013). The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells. Molecular Medicine Reports, 8, 557-564. https://doi.org/10.3892/mmr.2013.1551
MLA
Park, W. H."The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells". Molecular Medicine Reports 8.2 (2013): 557-564.
Chicago
Park, W. H."The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2‑treated HeLa cells". Molecular Medicine Reports 8, no. 2 (2013): 557-564. https://doi.org/10.3892/mmr.2013.1551
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