Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells

Carolyn J Fisher; Prabhat C Goswami

doi:10.4161/cbt.7.8.6300

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Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells

Journal article

Open access

Peer reviewed

Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells

Carolyn J Fisher and Prabhat C Goswami

Cancer biology & therapy, Vol.7(8), pp.1271-1279

08/2008

DOI: 10.4161/cbt.7.8.6300

PMCID: PMC2581876

PMID: 18497575

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Abstract

In recent years, cellular redox environment gained significant attention as a critical regulator of cellular responses to oxidative stress. Cellular redox environment is a balance between production of reactive oxygen species and their removal by antioxidant enzymes. We investigated the hypothesis that mitochondrial antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Vector-control and manganese superoxide dismutase (MnSOD) overexpressing human pancreatic cancer cells were irradiated and assayed for cell survival and activation of the G(2)-checkpoint pathway. Increased MnSOD activity significantly increased cell survival following irradiation with 6 Gy of gamma-radiation (p < 0.05). The MnSOD overexpressing irradiated cells also revealed 3-4 folds increase in the percentage of G(2) cells compared to irradiated vector-control. Furthermore, MnSOD overexpressing irradiated cells exhibited increased loss of phosphorylated histone H2AX protein levels. The radiation-induced increase in cyclin B1 protein levels in irradiated vector-control cells was suppressed in irradiated MnSOD overexpressing cells. Mitochondria-targeted catalase overexpression increased the survival of irradiated cells. These results support the hypothesis that mitochondrial antioxidant enzyme activity and mitochondria-generated reactive oxygen species-signaling (superoxide and hydrogen peroxide) could regulate radiation-induced G(2) checkpoint activation and radioresistance in human pancreatic cancer cells.

Mitochondria - enzymology

Pancreatic Neoplasms - metabolism

Reactive Oxygen Species - metabolism

Antioxidants - metabolism

Gene Expression Regulation, Enzymologic - radiation effects

Humans

Pancreatic Neoplasms - enzymology

Radiation Tolerance - genetics

Pancreatic Neoplasms - genetics

Mitochondria - metabolism

Cell Survival - radiation effects

Cyclin B1

Catalase - metabolism

Mitochondria - genetics

Models, Biological

Radiation Tolerance - physiology

Cyclin B - metabolism

Gene Expression Regulation, Neoplastic - radiation effects

Tumor Cells, Cultured

Dose-Response Relationship, Radiation

Superoxide Dismutase - metabolism

Details

Title: Subtitle: Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells
Creators: Carolyn J Fisher - Free Radical and Radiation Biology Program, Radiation Oncology Department, University of Iowa, Iowa City, Iowa 52242, USA
Prabhat C Goswami
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.7(8), pp.1271-1279
Publisher: United States
DOI: 10.4161/cbt.7.8.6300
PMID: 18497575
PMCID: PMC2581876
ISSN: 1538-4047
eISSN: 1555-8576
Grant note: CA078586-0651 / NCI NIH HHS CA111365 / NCI NIH HHS R01 CA111365-01A2 / NCI NIH HHS R01 CA111365 / NCI NIH HHS
Language: English
Date published: 08/2008
Academic Unit: Radiation Oncology
Record Identifier: 9984047698502771

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