The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Combination of carboplatin and intermittent normobaric hyperoxia synergistically suppresses benzo[a]pyrene-induced lung cancer

  • Lee, Hea Yon (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Kim, In Kyoung (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Lee, Hye In (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Lee, Hwa Young (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Kang, Hye Seon (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Yeo, Chang Dong (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Kang, Hyun Hui (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Moon, Hwa Sik (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sang Haak (Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea)
  • Received : 2016.11.02
  • Accepted : 2017.05.24
  • Published : 2018.05.01
⟨ Previous Next ⟩

Abstract

Background/Aims: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. Methods: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. Results: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. Conclusions: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF), The catholic University of Korea, St. Paul's Hospital

References

  1. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001;93:266-276. https://doi.org/10.1093/jnci/93.4.266
  2. Rofstad EK, Gaustad JV, Egeland TA, Mathiesen B, Galappathi K. Tumors exposed to acute cyclic hypoxic stress show enhanced angiogenesis, perfusion and metastatic dissemination. Int J Cancer 2010;127:1535-1546. https://doi.org/10.1002/ijc.25176
  3. Brizel DM, Lin S, Johnson JL, Brooks J, Dewhirst MW, Piantadosi CA. The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation. Br J Cancer 1995;72:1120-1124. https://doi.org/10.1038/bjc.1995.474
  4. Kalns J, Krock L, Piepmeier E Jr. The effect of hyperbaric oxygen on growth and chemosensitivity of metastatic prostate cancer. Anticancer Res 1998;18:363-367.
  5. Kunugita N, Kohshi K, Kinoshita Y, et al. Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models. Cancer Lett 2001;164:149-154. https://doi.org/10.1016/S0304-3835(00)00721-7
  6. Al-Waili NS, Butler GJ, Beale J, Hamilton RW, Lee BY, Lucas P. Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy. Med Sci Monit 2005;11:RA279-RA289.
  7. Takiguchi N, Saito N, Nunomura M, et al. Use of 5-FU plus hyperbaric oxygen for treating malignant tumors: evaluation of antitumor effect and measurement of 5-FU in individual organs. Cancer Chemother Pharmacol 2001;47:11-14. https://doi.org/10.1007/s002800000190
  8. Stuhr LE, Iversen VV, Straume O, Maehle BO, Reed RK. Hyperbaric oxygen alone or combined with 5-FU attenuates growth of DMBA-induced rat mammary tumors. Cancer Lett 2004;210:35-40. https://doi.org/10.1016/j.canlet.2004.02.012
  9. Raa A, Stansberg C, Steen VM, Bjerkvig R, Reed RK, Stuhr LE. Hyperoxia retards growth and induces apoptosis and loss of glands and blood vessels in DMBA-induced rat mammary tumors. BMC Cancer 2007;7:23. https://doi.org/10.1186/1471-2407-7-23
  10. Lindenschmidt RC, Margaretten N, Griesemer RA, Witschi HP. Modification of lung tumor growth by hyperoxia. Carcinogenesis 1986;7:1581-1586. https://doi.org/10.1093/carcin/7.9.1581
  11. Margaretten NC, Witschi H. Effects of hyperoxia on growth characteristics of metastatic murine tumors in the lung. Cancer Res 1988;48:2779-2783.
  12. Schuller HM, Witschi HP, Nylen E, Joshi PA, Correa E, Becker KL. Pathobiology of lung tumors induced in hamsters by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the modulating effect of hyperoxia. Cancer Res 1990;50:1960-1965.
  13. Petre PM, Baciewicz FA Jr, Tigan S, Spears JR. Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model. J Thorac Cardiovasc Surg 2003;125:85-95. https://doi.org/10.1067/mtc.2003.90
  14. Gill AL, Bell CN. Hyperbaric oxygen: its uses, mechanisms of action and outcomes. QJM 2004;97:385-395.
  15. Kallet RH, Matthay MA. Hyperoxic acute lung injury. Respir Care 2013;58:123-141. https://doi.org/10.4187/respcare.01963
  16. Konsavage WM, Zhang L, Wu Y, Shenberger JS. Hyperoxia-induced activation of the integrated stress response in the newborn rat lung. Am J Physiol Lung Cell Mol Physiol 2012;302:L27-L35. https://doi.org/10.1152/ajplung.00174.2011
  17. Balestra C, Germonpre P, Poortmans JR, Marroni A. Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the "normobaric oxygen paradox". J Appl Physiol (1985) 2006;100:512-518. https://doi.org/10.1152/japplphysiol.00964.2005
  18. Haddad JJ. Oxygen-sensing mechanisms and the regulation of redox-responsive transcription factors in development and pathophysiology. Respir Res 2002;3:26. https://doi.org/10.1186/rr191
  19. Narkowicz CK, Vial JH, McCartney PW. Hyperbaric oxygen therapy increases free radical levels in the blood of humans. Free Radic Res Commun 1993;19:71-80. https://doi.org/10.3109/10715769309056501
  20. Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 1990;186:1-85.
  21. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 1991;91:14S-22S.
  22. Oberley LW, Buettner GR. Role of superoxide dismutase in cancer: a review. Cancer Res 1979;39:1141-1149.
  23. Michiels C, Raes M, Toussaint O, Remacle J. Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 1994;17:235-248. https://doi.org/10.1016/0891-5849(94)90079-5
  24. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527-605. https://doi.org/10.1152/physrev.1979.59.3.527
  25. Jones DP, Eklow L, Thor H, Orrenius S. Metabolism of hydrogen peroxide in isolated hepatocytes: relative contributions of catalase and glutathione peroxidase in decomposition of endogenously generated H2O2. Arch Biochem Biophys 1981;210:505-516. https://doi.org/10.1016/0003-9861(81)90215-0
  26. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003;329:23-38. https://doi.org/10.1016/S0009-8981(03)00003-2
  27. Cheng KC, Cahill DS, Kasai H, Nishimura S, Loeb LA. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions. J Biol Chem 1992;267:166-172.
  28. Finkel T. Oxidant signals and oxidative stress. Curr Opin Cell Biol 2003;15:247-254. https://doi.org/10.1016/S0955-0674(03)00002-4
  29. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990;348:334-336. https://doi.org/10.1038/348334a0
  30. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993;74:609-619. https://doi.org/10.1016/0092-8674(93)90509-O
  31. Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999;6:99-104. https://doi.org/10.1038/sj.cdd.4400476

Cited by

  1. Systemic Evaluation on the Pharmacokinetics of Platinum-Based Anticancer Drugs From Animal to Cell Level: Based on Total Platinum and Intact Drugs vol.10, pp.None, 2020, https://doi.org/10.3389/fphar.2019.01485
  2. Hyperoxia Alters Ultrastructure and Induces Apoptosis in Leukemia Cell Lines vol.10, pp.2, 2018, https://doi.org/10.3390/biom10020282
  3. Role of hyperoxic treatment in cancer vol.245, pp.10, 2018, https://doi.org/10.1177/1535370220921547
  4. Repurposing of sildenafil as antitumour; induction of cyclic guanosine monophosphate/protein kinase G pathway, caspase-dependent apoptosis and pivotal reduction of Nuclear factor kappa light chain enh vol.73, pp.8, 2021, https://doi.org/10.1093/jpp/rgab049