Previously, we demonstrated that A549, a human lung cancer cell line, could be adapted to the free radical nitric oxide (NO •). NO • is known to be over expressed in human tumors. The original cell line, A549 (parent), and the newly adapted A549-HNO (which has a more aggressive phenotype) serve as a useful model system to study the biology of NO •. To see if tumor cells can similarly be adapted to any free radical with the same outcome, herein we successfully adapted A549 cells to high levels of hydrogen peroxide (HHP). A549-HHP, the resulting cell line, was more resistant and grew better then the parent cell line, and showed the following characteristics: (1) resistance to hydrogen peroxide, (2) resistance to NO •, (3) growth with and without hydrogen peroxide, and (4) resistance to doxorubicin. Gene chip analysis was used to determine the global gene expression changes between A549-parent and A549-HHP and revealed significant changes in the expression of over 1,700 genes. This gene profile was markedly different from that obtained from the A549-HNO cell line. The mitochondrial DNA content of the A549-HHP line determined by quantitative PCR favored a change for a more anaerobic metabolic profile. Our findings suggest that any free radical can induce resistance to other free radicals; this is especially important given that radiation therapy and many chemotherapeutic agents exert their effect via free radicals. Utilizing this model system to better understand the role of free radicals in tumor biology will help to develop new therapeutic approaches to treat lung cancer. © International Society of Oncology and BioMarkers (ISOBM) 2012

Onul, A., Elseth, K., DE VITTO, H., Paradise, W., Vesper, B., Tarjan, G., et al. (2012). Long-term adaptation of the human lung tumor cell line A549 to increasing concentrations of hydrogen peroxide. TUMOR BIOLOGY, 33(3), 739-748 [10.1007/s13277-011-0271-5].

Long-term adaptation of the human lung tumor cell line A549 to increasing concentrations of hydrogen peroxide

DE VITTO, HUMBERTO
Secondo
;
2012

Abstract

Previously, we demonstrated that A549, a human lung cancer cell line, could be adapted to the free radical nitric oxide (NO •). NO • is known to be over expressed in human tumors. The original cell line, A549 (parent), and the newly adapted A549-HNO (which has a more aggressive phenotype) serve as a useful model system to study the biology of NO •. To see if tumor cells can similarly be adapted to any free radical with the same outcome, herein we successfully adapted A549 cells to high levels of hydrogen peroxide (HHP). A549-HHP, the resulting cell line, was more resistant and grew better then the parent cell line, and showed the following characteristics: (1) resistance to hydrogen peroxide, (2) resistance to NO •, (3) growth with and without hydrogen peroxide, and (4) resistance to doxorubicin. Gene chip analysis was used to determine the global gene expression changes between A549-parent and A549-HHP and revealed significant changes in the expression of over 1,700 genes. This gene profile was markedly different from that obtained from the A549-HNO cell line. The mitochondrial DNA content of the A549-HHP line determined by quantitative PCR favored a change for a more anaerobic metabolic profile. Our findings suggest that any free radical can induce resistance to other free radicals; this is especially important given that radiation therapy and many chemotherapeutic agents exert their effect via free radicals. Utilizing this model system to better understand the role of free radicals in tumor biology will help to develop new therapeutic approaches to treat lung cancer. © International Society of Oncology and BioMarkers (ISOBM) 2012
Articolo in rivista - Articolo scientifico
Adenocarcinoma; Cellular adaptation; Cross-resistance; Hydrogen peroxide; Lung cancer; Nitric oxide; Reactive oxygen species (ROS); Adenocarcinoma; Cell Line, Tumor; Cell Proliferation; DNA, Mitochondrial; Doxorubicin; Drug Resistance; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Hydrogen Peroxide; Lung Neoplasms; Adaptation, Physiological; Cancer Research; Medicine (all)
English
2012
33
3
739
748
open
Onul, A., Elseth, K., DE VITTO, H., Paradise, W., Vesper, B., Tarjan, G., et al. (2012). Long-term adaptation of the human lung tumor cell line A549 to increasing concentrations of hydrogen peroxide. TUMOR BIOLOGY, 33(3), 739-748 [10.1007/s13277-011-0271-5].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/106964
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