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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation

  • Authors:
    • Mizuki Tochigi
    • Toshio Inoue
    • Miki Suzuki-Karasaki
    • Toyoko Ochiai
    • Chisei Ra
    • Yoshihiro Suzuki-Karasaki
  • View Affiliations / Copyright

    Affiliations: Division of Molecular Cell Immunology and Allergology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan, Department of Dermatology, Nihon University Surugadai Hospital, Tokyo, Japan
  • Pages: 863-872
    |
    Published online on: January 10, 2013
       https://doi.org/10.3892/ijo.2013.1769
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Abstract

Intracellular reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) are thought to mediate apoptosis induced by death receptor ligands, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). However, the role of H2O2 is controversial, since some evidence suggests that H2O2 acts as an anti-apoptotic factor. Here, we show that exogenously applied H2O2 (30‑100 µM) induces cell death in TRAIL-resistant human melanoma cells via intracellular superoxide (O2-) generation. H2O2 induced apoptotic or necrotic cell death, depending on the concentration of the oxidant applied; low concentrations of H2O2 preferentially activated the caspase-dependent apoptotic pathway, while high concentrations of H2O2 induced apoptotic and necrotic cell death in a caspase-independent manner. The H2O2-induced cell death was associated with increased mitochondrial membrane potential collapse and caspase-3/7 activation and ER stress responses including caspase-12 and X-box-binding protein-1 (XBP-1) activation. H2O2 induced intracellular O2- generation even within the mitochondria, while TRAIL did not. The superoxide dismutase mimetic antioxidant MnTBaP [Mn (III) tetrakis (4-benzonic acid) porphyrin chloride] inhibited the H2O2‑induced O2- generation, apoptosis and XBP-1 and caspase-12 activation at comparable concentrations. Importantly, H2O2 treatment caused minimal O2- generation and apoptosis in normal primary melanocytes. These data show that H2O2 induces endoplasmic reticulum-associated cell death via intracellular O2- generation and that malignant melanoma cells are more susceptible than normal cells to this oxidative cell death. The findings suggest that H2O2 has therapeutic potential in the treatment of TRAIL‑resistant melanoma.
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1 

Dyer MJ, MacFarlane M and Cohen GM: Barriers to effective TRAIL-targeted therapy of malignancy. J Clin Oncol. 25:4505–4506. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Johnstone RW, Frew AJ and Smyth MJ: The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 8:782–798. 2008. View Article : Google Scholar : PubMed/NCBI

3 

LeBlanc HN and Ashkenazi A: Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ. 10:66–75. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Wang S: The promise of cancer therapeutics targeting the TNF-related apoptosis-inducing ligand and TRAIL receptor pathway. Oncogene. 27:6207–6215. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Sayers TJ: Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunol Immunother. 60:1173–1180. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Dimberg LY, Anderson CK, Camidge R, Behbakht K, Thorburn A and Ford HL: On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics. Oncogene. May 14–2012.(Epub ahead of print). View Article : Google Scholar

7 

Circu ML and Aw TY: Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 48:749–762. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Fas SC, Baumann S, Zhu JY, et al: Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis. Blood. 108:3700–3706. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Shenoy K, Wu Y and Pervaiz S: LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors. Cancer Res. 69:1941–1950. 2009. View Article : Google Scholar

10 

Barbouti A, Amorgianiotis C, Kolettas E, Kanavaros P and Galaris D: Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Radic Biol Med. 43:1377–1387. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Choi K, Ryu SW, Song S, Choi H, Kang SW and Choi C: Caspase-dependent generation of reactive oxygen species in human astrocytoma cells contributes to resistance to TRAIL-mediated apoptosis. Cell Death Differ. 17:833–845. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Suzuki Y, Inoue T, Murai M, et al: Depolarization potentiates TRAIL-induced apoptosis in human melanoma cells: role for ATP-sensitive K+ channels and endoplasmic reticulum stress. Int J Oncol. 41:465–475. 2012.PubMed/NCBI

13 

Suzuki Y, Yoshimaru T, Inoue T and Ra C: Mitochondrial Ca2+ flux is a critical determinant of the Ca2+ dependence of mast cell degranulation. J Leukoc Biol. 79:508–518. 2006.

14 

Inoue T, Suzuki Y, Yoshimaru T and Ra C: Reactive oxygen species produced up-or downstreame of calcium influx regulate proinflammatory mediator release from mast cells: role of NADPH oxidase and mitochondria. Biochem Biophys Acta. 1783:789–802. 2008. View Article : Google Scholar

15 

Robinson KM, Janes MS, Pehar M, et al: Selective fluorescencet imaging of superoxide in vivo using ethidium-based probes. Proc Natl Acad Sci USA. 103:15038–15043. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Carter WO, Narayanan PK and Robinson JP: Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells. J Leukoc Biol. 55:253–258. 1994.PubMed/NCBI

17 

Devadas S, Hinshaw JA, Zaritskaya L and Williams MS: Fas-stimulated generation of reactive oxygen species or exogenous oxidative stress sensitize cells to Fas-mediated apoptosis. Free Radic Biol Med. 35:648–661. 2003. View Article : Google Scholar

18 

Suzuki Y, Yoshimaru T, Inoue T and Ra C: Discrete generations of intracellular hydrogen peroxide and superoxide in antigen-stimulated mast cells: reciprocal regulation of store-operated Ca2+ channel activity. Mol Immunol. 46:2200–2209. 2009. View Article : Google Scholar

19 

Mukhopadhyay P, Rajesh M, Kashiwaya Y, Haskó G and Pacher P: Simple quantitative detection of mitochondrial superoxide production in live cells. Biochem Biophys Res Commun. 358:203–208. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Breckenridge DG, Germain M, Mathai JP, et al: Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 22:8608–8618. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Boyce M and Yuan J: Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ. 13:363–373. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Nakagawa T, Zhu H, Morishima N, et al: Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 403:98–103. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Groenendyk J and Michalak M: Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol. 52:381–395. 2005.PubMed/NCBI

24 

Rao RV, Castro-Obregon S, Frankowski H, et al: Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J Biol Chem. 277:21836–21842. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Morishima N, Nakanishi K, Takenouchi H, Shibata T and Yasuhiko Y: An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem. 277:34287–34294. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Szegezdi E, Fitzgerald U and Samali A: Caspase-12 and ER-stress-mediated apoptosis: the story so far. Ann NY Acad Sci. 1010:186–194. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Fischer H, Koenig U, Eckhart L and Tschachler E: Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun. 293:722–726. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Pallepati P and Averill-Bates DA: Activation of ER stress and apoptosis by hydrogen peroxide in HeLa cells: protective role of mild heat preconditioning at 40°C. Biochim Biophys Acta. 12:1987–1999. 2011.PubMed/NCBI

29 

Mandic A, Hansson J, Linder S and Shoshan MC: Cisplatin induces endoplasmic reticulum stress and nucleus-independent apoptotic signaling. J Biol Chem. 278:9100–9106. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Tinhofer I, Anether G, Senfter M, et al: Stressful death of T-ALL tumor cells after treatment with the anti-tumor agent Tetrocarcin-A. FASEB J. 16:1295–1297. 2002.PubMed/NCBI

31 

Xie Q, Khaoustov VI, Chung CC, et al: Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation. Hepatology. 36:592–601. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Trisciuoglio D, Uranchimeg B, Cardellina JH, et al: Induction of apoptosis in human cancer cells by candidaspongiolide, a novel sponge polyketide. J Natl Cancer Inst. 100:1233–1246. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Shellman Y, Howe WR, Miller LA, et al: Hyperthermia induces endoplasmic reticulum-mediated apoptosis in melanoma and non-melanoma skin cancer cells. J Invest Dermatol. 128:949–956. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Hersey P and Zhang XD: Adaptation to ER stress as a driver of malignancy and resistance to therapy in human melanoma. Pigment Cell Melanoma Res. 21:358–367. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Rutkowski DT and Kaufman RJ: That which does not kill me makes me stronger: adapting to chronic ER stress. Trends Biochem Sci. 32:469–476. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Jiang CC, Mao ZG, Avery-Kiejda KA, Wade M, Hersey P and Zhang XD: Glucose-regulated protein 78 antagonizes cisplatin and adriamycin in human melanoma cells. Carcinogenesis. 30:197–204. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tochigi M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C and Suzuki-Karasaki Y: Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation. Int J Oncol 42: 863-872, 2013.
APA
Tochigi, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., & Suzuki-Karasaki, Y. (2013). Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation. International Journal of Oncology, 42, 863-872. https://doi.org/10.3892/ijo.2013.1769
MLA
Tochigi, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Suzuki-Karasaki, Y."Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation". International Journal of Oncology 42.3 (2013): 863-872.
Chicago
Tochigi, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Suzuki-Karasaki, Y."Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation". International Journal of Oncology 42, no. 3 (2013): 863-872. https://doi.org/10.3892/ijo.2013.1769
Copy and paste a formatted citation
x
Spandidos Publications style
Tochigi M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C and Suzuki-Karasaki Y: Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation. Int J Oncol 42: 863-872, 2013.
APA
Tochigi, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., & Suzuki-Karasaki, Y. (2013). Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation. International Journal of Oncology, 42, 863-872. https://doi.org/10.3892/ijo.2013.1769
MLA
Tochigi, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Suzuki-Karasaki, Y."Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation". International Journal of Oncology 42.3 (2013): 863-872.
Chicago
Tochigi, M., Inoue, T., Suzuki-Karasaki, M., Ochiai, T., Ra, C., Suzuki-Karasaki, Y."Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation". International Journal of Oncology 42, no. 3 (2013): 863-872. https://doi.org/10.3892/ijo.2013.1769
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