title: 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 peroxiredoxin-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.
authors.affiliation: Laboratorio de Nanomedicina, Comisión Nacional de Energía Atómica, Av. General Paz 1499, San Martin, Buenos Aires, Argentina. Electronic address: belencerda@cnea.gov.ar.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Cerda
authors.affiliation: Laboratorio de Nanomedicina, Comisión Nacional de Energía Atómica, Av. General Paz 1499, San Martin, Buenos Aires, Argentina.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lloyd
authors.affiliation: Laboratorio de Nanomedicina, Comisión Nacional de Energía Atómica, Av. General Paz 1499, San Martin, Buenos Aires, Argentina.
authors.forename: Milena
authors.initials: M
authors.lastname: Batalla
authors.affiliation: Laboratorio de Nanomedicina, Comisión Nacional de Energía Atómica, Av. General Paz 1499, San Martin, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Giannoni
authors.affiliation: Instituto de Oncología Angel H. Roffo, Universidad de Buenos Aires, Av. San Martín 5481, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Casal
authors.affiliation: Laboratorio de Nanomedicina, Comisión Nacional de Energía Atómica, Av. General Paz 1499, San Martin, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: policast@cnea.gov.ar.
authors.forename: Lucia
authors.initials: L
authors.lastname: Policastro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000077150:Oxaliplatin; D054464:Peroxiredoxins / Q000378:metabolism*; D011839:Radiation, Ionizing
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D054464:Peroxiredoxins
keywords: Colorectal cancer; Oxaliplatin; Peroxiredoxin 2; Radiation sensitivity