Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications

R. Gogna, E. Madan, P. Kuppusamy, U. Pati

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Hypoxic tumors are resistant to conventional therapies through indirect mechanisms such as the selection of resistant phenotype under chronic hypoxia. Hyperbaric oxygen (HBO) therapy has been shown to increase oxygen level and induce apoptosis in hypoxic tumor. However, it could produce significant adverse effects including oxygen toxic seizures and severe radiation tissue injury due to high pressure. We have shown that repeated oxygenation at 30% O 2 (1 atmospheres absolute) results in significant regression of MCF-7 tumor xenografts without any adverse effect. In MCF-7 cells, re-oxygenation showed an eightfold increase in cellular apoptosis. Both in hypoxic tumor and in hypoxic cells, that exclusively favor p53 to exist in mutant conformation, re-oxygenation restores p53 wild-type conformation. The oxygen-mediated rescue of mutant p53 followed by its trans-activation is responsible for the induction of p53-downstream apoptotic, cell-cycle arrest and DNA-repair genes. Further, p53 trans-activation may thus be due to its post-translational modifications as a result of re-oxygenation. We have thus concluded that oxygen therapy without pressure, as opposed to HBO therapy, may be ideal for hypoxic tumor regression, which functions through oxygen-mediated rescue of mutant p53 followed by induction of apoptosis.

Original languageEnglish (US)
JournalCell Death and Disease
Volume3
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Post Translational Protein Processing
Oxygen
Hyperbaric Oxygenation
Neoplasms
Apoptosis
Pressure
Radiation Injuries
Poisons
MCF-7 Cells
Cell Cycle Checkpoints
Atmosphere
Heterografts
DNA Repair
Seizures
Phenotype
Therapeutics
Genes

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Cite this

Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications. / Gogna, R.; Madan, E.; Kuppusamy, P.; Pati, U.

In: Cell Death and Disease, Vol. 3, No. 3, 03.2012.

Research output: Contribution to journalArticle

@article{e17d9e33a24c4bf1be3dcc5c0711ebe0,
title = "Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications",
abstract = "Hypoxic tumors are resistant to conventional therapies through indirect mechanisms such as the selection of resistant phenotype under chronic hypoxia. Hyperbaric oxygen (HBO) therapy has been shown to increase oxygen level and induce apoptosis in hypoxic tumor. However, it could produce significant adverse effects including oxygen toxic seizures and severe radiation tissue injury due to high pressure. We have shown that repeated oxygenation at 30{\%} O 2 (1 atmospheres absolute) results in significant regression of MCF-7 tumor xenografts without any adverse effect. In MCF-7 cells, re-oxygenation showed an eightfold increase in cellular apoptosis. Both in hypoxic tumor and in hypoxic cells, that exclusively favor p53 to exist in mutant conformation, re-oxygenation restores p53 wild-type conformation. The oxygen-mediated rescue of mutant p53 followed by its trans-activation is responsible for the induction of p53-downstream apoptotic, cell-cycle arrest and DNA-repair genes. Further, p53 trans-activation may thus be due to its post-translational modifications as a result of re-oxygenation. We have thus concluded that oxygen therapy without pressure, as opposed to HBO therapy, may be ideal for hypoxic tumor regression, which functions through oxygen-mediated rescue of mutant p53 followed by induction of apoptosis.",
author = "R. Gogna and E. Madan and P. Kuppusamy and U. Pati",
year = "2012",
month = "3",
doi = "10.1038/cddis.2012.15",
language = "English (US)",
volume = "3",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications

AU - Gogna, R.

AU - Madan, E.

AU - Kuppusamy, P.

AU - Pati, U.

PY - 2012/3

Y1 - 2012/3

N2 - Hypoxic tumors are resistant to conventional therapies through indirect mechanisms such as the selection of resistant phenotype under chronic hypoxia. Hyperbaric oxygen (HBO) therapy has been shown to increase oxygen level and induce apoptosis in hypoxic tumor. However, it could produce significant adverse effects including oxygen toxic seizures and severe radiation tissue injury due to high pressure. We have shown that repeated oxygenation at 30% O 2 (1 atmospheres absolute) results in significant regression of MCF-7 tumor xenografts without any adverse effect. In MCF-7 cells, re-oxygenation showed an eightfold increase in cellular apoptosis. Both in hypoxic tumor and in hypoxic cells, that exclusively favor p53 to exist in mutant conformation, re-oxygenation restores p53 wild-type conformation. The oxygen-mediated rescue of mutant p53 followed by its trans-activation is responsible for the induction of p53-downstream apoptotic, cell-cycle arrest and DNA-repair genes. Further, p53 trans-activation may thus be due to its post-translational modifications as a result of re-oxygenation. We have thus concluded that oxygen therapy without pressure, as opposed to HBO therapy, may be ideal for hypoxic tumor regression, which functions through oxygen-mediated rescue of mutant p53 followed by induction of apoptosis.

AB - Hypoxic tumors are resistant to conventional therapies through indirect mechanisms such as the selection of resistant phenotype under chronic hypoxia. Hyperbaric oxygen (HBO) therapy has been shown to increase oxygen level and induce apoptosis in hypoxic tumor. However, it could produce significant adverse effects including oxygen toxic seizures and severe radiation tissue injury due to high pressure. We have shown that repeated oxygenation at 30% O 2 (1 atmospheres absolute) results in significant regression of MCF-7 tumor xenografts without any adverse effect. In MCF-7 cells, re-oxygenation showed an eightfold increase in cellular apoptosis. Both in hypoxic tumor and in hypoxic cells, that exclusively favor p53 to exist in mutant conformation, re-oxygenation restores p53 wild-type conformation. The oxygen-mediated rescue of mutant p53 followed by its trans-activation is responsible for the induction of p53-downstream apoptotic, cell-cycle arrest and DNA-repair genes. Further, p53 trans-activation may thus be due to its post-translational modifications as a result of re-oxygenation. We have thus concluded that oxygen therapy without pressure, as opposed to HBO therapy, may be ideal for hypoxic tumor regression, which functions through oxygen-mediated rescue of mutant p53 followed by induction of apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=84859371685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859371685&partnerID=8YFLogxK

U2 - 10.1038/cddis.2012.15

DO - 10.1038/cddis.2012.15

M3 - Article

VL - 3

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 3

ER -