Silencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin

Abstract Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of...

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Bibliographic Details
Published in:Cancer letters 2017-03, Vol.388, p.312-319
Main Authors: Cerda, María Belén, Lloyd, Rodrigo, Batalla, Milena, Giannoni, Florencia, Casal, Mariana, Policastro, Lucia
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer therapies
Cell growth
Cell Line, Tumor
Cell Proliferation
Cloning
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Conflicts of interest
Enzymes
Female
Genomes
Hematology, Oncology and Palliative Medicine
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Organoplatinum Compounds - pharmacology
Organoplatinum Compounds - therapeutic use
Oxaliplatin
Peroxiredoxin 2
Peroxiredoxins - metabolism
Radiation sensitivity
Radiation, Ionizing
Signal transduction
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Summary:Abstract Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of peroxirredoxin-2 (Prx2) in the radio and chemoradiotherapy response in CRC cells in vitro and in vivo. We found that Prx2 oxidation state is associated to differential response to ionizing radiation in CRC cell lines. HCT116 radioresistant CRC cell line have lower ROS levels and a higher monomer/dimer Prx2 ratio, compared to halfway resistant Caco-2 and T84, and radiosensitive LoVo cell line. Constitutive and transient Prx2 silencing in CRC cells increase ROS levels, and most importantly, enhance in vitro radiation sensitivity. In addition, we showed that administration of IR plus oxaliplatin in down regulated Prx2 HCT116 cells has higher citotoxic effect than in control cells. Finally, radiosensitizing effect of Prx2 depletion was confirmed in vivo . These results suggest that Prx2 is an important component in tumoral radiation response, and their inhibition could improve radio and chemoradiotherapy protocols in patients with CRC.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2016.12.009