Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis
Open accessAbstract
Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks. In addition, A549 lung cancer cells were incubated in a normobaric hyperoxia chamber for a 24-h period. As a result, the size and number of tumors in the lung decreased significantly with exposure to normobaric hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric hyperoxia and the normal control group exposed to normobaric hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric hyperoxia in cancer cells. A549 cells exposed to normobaric hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2 mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric hyperoxia in inhibiting lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-tumor effect of normobaric hyperoxia may due to the increased reactive oxygen species activity and apoptosis, which is related to the mitogen-activated protein kinase pathway. Impact statement: Normobaric hyperoxia (NBO) is a feasible therapy for cancer with a low complication rate. Although NBO may be beneficial in cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.
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The antitumor effect of atmospheric hyperoxia may be due to oxidative stress and increased apoptosis (Bax/Bcl-2 mRNA expression rate), associated with the MAPK pathway.
“The antitumor effect of atmospheric hyperoxia may be due to oxidative stress and increased apoptosis (BCL2‐associated X [Bax]/Bcl‐2 mRNA expression rate), which is associated with the mitogen‐activated protein kinase (MAPK) pathway.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [298]
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Cites
(1992) · Applied Ergonomics · doi:10.1016/0003-6870(92)90338-v · Cited by 7,153 · see citing works
[1] Role of free radicals and catalytic metal ions in human disease: An overview
Halliwell, B., & Gutteridge, J. M. C. (1990) · Methods in Enzymology · doi:10.1016/0076-6879(90)86093-b · Cited by 4,994 · see citing works
Oxidative Stress and Antioxidant Defense
Birben, E., Şahiner, Ü. M., Saçkesen, C., ERZURUM, S. C., & Kalaycı, Ö. (2012) · World Allergy Organization Journal · doi:10.1097/wox.0b013e3182439613 · Cited by 4,960 · see citing works
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579 · see citing works
Role of reactive oxygen species (ROS) in apoptosis induction
Simon, H.-U., Haj-Yehia, A., & Levi-Schaffer, F. (2000) · Apoptosis · doi:10.1023/a:1009616228304 · Cited by 2,774 · see citing works
Mitochondria, oxidative stress and cell death
Ott, M., Gogvadze, V. G., Orrenius, S., & Zhivotovsky, B. (2007) · APOPTOSIS · doi:10.1007/s10495-007-0756-2 · Cited by 1,976 · see citing works
Bax directly induces release of cytochrome c from isolated mitochondria
Jürgensmeier, J. M., Xie, Z., Deveraux, Q. L., Ellerby, L., Bredesen, D. E., & Reed, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.4997 · Cited by 1,523 · see citing works
Mitogen-activated protein kinases in apoptosis regulation
Wada, T., & Penninger, J. M. (2004) · Oncogene · doi:10.1038/sj.onc.1207556 · Cited by 1,432 · see citing works
Oxidant signals and oxidative stress
Finkel, T. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00002-4 · Cited by 1,393 · see citing works
ROS homeostasis and metabolism: a dangerous liason in cancer cells
Panieri, E., & Santoro, M. M. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.105 · Cited by 1,156 · see citing works
Oxidative stress: the paradox of aerobic life
Davies, K. J. A. (1995) · Biochemical Society Symposia · doi:10.1042/bss0610001 · Cited by 1,150 · see citing works
Maxwell, P. H., Dachs, G. U., Gleadle, J. M., Nicholls, L. G., Harris, A. L., Stratford, I. J., Hankinson, O., Pugh, C. W., & Ratcliffe, P. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8104 · Cited by 1,084 · see citing works
Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies
Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., & Toomey, D. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00003-3 · Cited by 559 · see citing works
Hypoxia and Radiation Therapy: Past History, Ongoing Research, and Future Promise
Rockwell, S., Dobrucki, I. T., Kim, E. Y., Marrison, S. T., & Vu, V. (2009) · Current Molecular Medicine · doi:10.2174/156652409788167087 · Cited by 512 · see citing works
Kallet, R. H., & Matthay, M. A. (2013) · Respiratory Care · doi:10.4187/respcare.01963 · Cited by 438 · see citing works
Ballif, B. A., & Blenis, J. (2001) · PubMed · Cited by 419 · see citing works
Morphologic Changes in Pulmonary Oxygen Toxicity
Crapo, J. D. (1986) · Annual Review of Physiology · doi:10.1146/annurev.ph.48.030186.003445 · Cited by 405 · see citing works
Classification of Proliferative Pulmonary Lesions of the Mouse
Nikitin, A. Y., Alcaraz, A., Anver, M. R., Bronson, R. T., Cardiff, R. D., Dixon, D., Fraire, A. E., Gabrielson, E. W., Gunning, W. T., Haines, D. C., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3376 · Cited by 334 · see citing works
Axelson, H., Fredlund, E., Ovenberger, M., Landberg, G., & Påhlman, S. (2005) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2005.03.007 · Cited by 306 · see citing works
Hyperbaric oxygen therapy and cancer—a review
Moen, I. N., & Stuhr, L. E. B. (2012) · Targeted Oncology · doi:10.1007/s11523-012-0233-x · Cited by 304 · see citing works
Complications and side effects of hyperbaric oxygen therapy.
Plafki, C., Peters, P., Almeling, M., Welslau, W., & Busch, R. (2000) · PubMed · Cited by 280 · see citing works
Regulation of Proliferation-Survival Decisions during Tumor Cell Hypoxia
Schmaltz, C., Hardenbergh, P. H., Wells, A. G., & Fisher, D. E. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.5.2845 · Cited by 217 · see citing works
Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung
Mach, W. J., Thimmesch, A. R., Pierce, J. T., & Pierce, J. D. (2011) · Nursing Research and Practice · doi:10.1155/2011/260482 · Cited by 215 · see citing works
Rockswold, S. B., Rockswold, G., Zaun, D., Zhang, X., Cerra, C., Bergman, T. A., & Liu, J.-N. (2010) · Journal of Neurosurgery · doi:10.3171/2009.7.jns09363 · Cited by 208 · see citing works
Increased Oxidative Stress as a Selective Anticancer Therapy
Liu, J., & Wang, Z. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/294303 · Cited by 184 · see citing works
Stem-like Cancer Cells Are Inducible by Increasing Genomic Instability in Cancer Cells
Liang, Y., Zhong, Z. A., Huang, Y., Deng, W., Cao, J., Tsao, G. S., Liu, Q., Pei, D., Kang, T., & Zeng, Y. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.048397 · Cited by 117 · see citing works
Raa, A., Stansberg, C. T., Steen, V. M., Bjerkvig, R., Reed, R. K., & Stuhr, L. E. B. (2007) · BMC Cancer · doi:10.1186/1471-2407-7-23 · Cited by 77 · see citing works
The Hypoxic Tumour Microenvironment, Patient Selection and Hypoxia-modifying Treatments
Hoogsteen, I. J., Marres, H. A. M., van der Kogel, A. J., & Kaanders, J. H. A. M. (2007) · Clinical Oncology · doi:10.1016/j.clon.2007.03.001 · Cited by 77 · see citing works
Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model
Moen, I. N., Oyan, A. M., Kalland, K.-H., Tronstad, K. J., Akslen, L. A., Chekenya, M., Sakariassen, P. Ø., Reed, R. K., & Stuhr, L. E. B. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006381 · Cited by 76 · see citing works
Stuhr, L. E. B., Raa, A., Øyan, A. M., Kalland, K. H., Sakariassen, P. O., Petersen, K., Bjerkvig, R., & Reed, R. K. (2007) · Journal of Neuro-Oncology · doi:10.1007/s11060-007-9407-2 · Cited by 76 · see citing works
Shi, S., Qi, Z., Ma, Q., et al. (2017) · Stroke · doi:10.1161/strokeaha.117.017713 · Cited by 76 · see citing works
Avisetti, D. R., Babu, K. S., & Kalivendi, S. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087050 · Cited by 69 · see citing works
Liu, W., Hendren, J. D., Qin, X.-J., & Liu, K. J. (2009) · Stroke · doi:10.1161/strokeaha.108.545483 · Cited by 62 · see citing works
Moen, I., Tronstad, K. J., Kolmannskog, O., Salvesen, G. S., Reed, R. K., & Stuhr, L. E. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-446 · Cited by 49 · see citing works
Oxygenation inhibits ovarian tumor growth by down-regulating STAT3 and cyclin-D1 expressions
Selvendiran, K., Kuppusamy, M. L., Ahmed, S., Bratasz, A., Meenakshisundaram, G., Rivera, B. K., Khan, M., & Kuppusamy, P. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.4.12448 · Cited by 46 · see citing works
Effect of Hypoxia on the Tumor Phenotype: The Neuroblastoma and Breast Cancer Models
Mengelbier, L. H., Löfstedt, T., & Påhlman, S. (2006) · Advances in experimental medicine and biology · doi:10.1007/978-1-4020-5133-3_16 · Cited by 44 · see citing works
Ejaz, S., Emmrich, J., Sitnikov, S., Hong, Y. T., Sawiak, S. J., Fryer, T. D., Aigbirhio, F. I., Williamson, D. J., & Baron, J. (2016) · Brain · doi:10.1093/brain/awv391 · Cited by 40 · see citing works
Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective
Ji, X., Liu, K., Shi, S., et al. (2016) · Medical Gas Research · doi:10.4103/2045-9912.191360 · Cited by 33 · see citing works
Makena, P. S., Gorantla, V. K., Ghosh, M. C., et al. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00539.2011 · Cited by 26 · see citing works
Zhu, Q., Hu, J., Meng, H., Shen, Y., Zhou, J., & Zhu, Z. (2014) · International Journal of Gynecological Cancer · doi:10.1097/igc.0000000000000105 · Cited by 21 · see citing works
Oxygen treatment triggers cognitive impairment in Alzheimer's transgenic mice
Arendash, G. W., Cox, A., Mori, T., Cracchiolo, J. R., Hensley, K., & Roberts, L. J. (2009) · Neuroreport · doi:10.1097/wnr.0b013e32832e6459 · Cited by 20 · see citing works
Hyperbaric oxygen therapy and squamous cell carcinoma cell line growth
Sklizovic, D., Sanger, J. R., Kindwall, E. P., et al. (1993) · Head & Neck · doi:10.1002/hed.2880150311 · Cited by 20 · see citing works
The Enhancing Effects of Hyperbaric Oxygen on Mouse Skin Carcinogenesis
Doguchi, H., Saio, M., Kuniyoshi, S., et al. (2014) · Journal of Toxicologic Pathology · doi:10.1293/tox.2013-0046 · Cited by 9 · see citing works
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Hypoxia signaling in cancer: Implications for therapeutic interventions
Zhuang, Y., Liu, K., He, Q., Gu, X., Jiang, C., & Wu, J. (2023) · MedComm · doi:10.1002/mco2.203 · Cited by 119 · see citing works
Herrera-Campos, A. B., Zamudio-Martinez, E., Delgado-Bellido, D., Fernández-Cortés, M., Montuenga, L. M., Oliver, F. J., & Garcia-Diaz, A. (2022) · Cancers · doi:10.3390/cancers14112740 · Cited by 17 · see citing works
- Authors
- Kim, S. W., Kim, I. K., Ha, J. H., Yeo, C. D., Kang, H. H., Kim, J. W., & Lee, S. H.
- Affiliations
- St. Paul's Hospital (KR)
- The Catholic University of Korea Incheon St. Mary's Hospital (KR)
- The Catholic University of Korea Uijeongbu St. Mary's Hospital (KR)
- Corresponding author
- Lee, Sang Haak
- Venue
- Experimental Biology and Medicine
- Publisher
- Frontiers Media SA
- Published
- 2018-05
- Volume
- 243
- Issue
- 9
- Pages
- 739-748
- ISSN
- 0071-3384 (ISSN-L)
- 1535-3702
- 1535-3699
- PMC
- PMC5956666
- OpenAlex
- W2803697852
- Cited by
- 25
- References
- 43
- Citations by year
- 2024: 2 · 2023: 7 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Biology and Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Catholic University of Korea
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- normobaric hyperoxia, lung cancer, apoptosis, tumor hypoxia, oxidative stress, reactive oxygen species, Bax/Bcl-2 ratio, ERK, JNK, MAPK signaling, Lewis lung carcinoma, A549 cells, tumor cell migration and invasion, anti-tumor therapy
- MeSH terms
- A549 Cells, Animals, Humans, Lung Neoplasms, Male, Oxygen, Gene Expression Regulation, Neoplastic, Apoptosis, Oxidative Stress, Hyperoxia, Carcinoma, Lewis Lung, Proto-Oncogene Proteins c-bcl-2, bcl-2-Associated X Protein, Mice
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