Journal article
Increased activator protein 1 activity as well as resistance to heat-induced radiosensitization, hydrogen peroxide, and cisplatin are inhibited by indomethacin in oxidative stress-resistant cells
Cancer research (Chicago, Ill.), Vol.61(8), pp.3486-3492
2001
PMID: 11309312
Abstract
It has been established that tumor cells develop resistance to a variety of therapeutic agents after multiple exposures to these agents/drugs. Many of these therapeutic agents also appear to increase the activity of transcription factors, such as activator protein 1 (AP-1), believed to be involved in cellular responses to oxidative stress. Therefore, we hypothesized that cellular resistance to cancer therapeutic agents may involve the increased activity of transcription factors that govern resistance to oxidative stress, such as AP-1. To investigate this hypothesis, a previously characterized cisplatin, hyperthermia, and oxidative stress-resistant Chinese hamster fibroblast cell line, OC-14, was compared to the parental HA-1 cell line. Electrophoretic mobility shift and Western blot assays performed on extracts isolated from OC-14 cells demonstrated a 10-fold increase in constitutive AP-1 DNA-binding activity as well as increased constitutive c-Fos and c-Jun immunoreactive protein relative to HA-1 cells. Treatment of OC-14 cells with indomethacin inhibited constitutive increases in AP-1 DNA-binding activity and c-Fos/c-Jun-immunoreactive protein levels. Clonogenic survival assays demonstrated that pretreatment with indomethacin, at concentrations that inhibited AP-1 activity, significantly reduced the resistance of OC-14 cells to heat-induced radiosensitization, hydrogen peroxide, and cisplatin. These results demonstrate a relationship between increases in AP-1 DNA-binding activity and increased cellular resistance to cancer therapeutic agents and oxidative stress that is inhibited by indomethacin. These results support the hypothesis that inhibition of AP-1 activity with nonsteroidal anti-inflammatory drugs, such as indomethacin, may represent a useful adjuvant to cancer therapy.
Details
- Title: Subtitle
- Increased activator protein 1 activity as well as resistance to heat-induced radiosensitization, hydrogen peroxide, and cisplatin are inhibited by indomethacin in oxidative stress-resistant cells
- Creators
- C. Matthew Bradbury - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United StatesJacob E Locke - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United StatesS. Jack Wei - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United StatesLuis M Rene - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United StatesShervin Karimpour - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United StatesClayton Hunt - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United StatesDouglas R Spitz - University of IowaDavid Gius - Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63108, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.61(8), pp.3486-3492
- Publisher
- American Association for Cancer Research
- PMID
- 11309312
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2001
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984313077202771
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