Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells to gamma-Radiation by Attenuating DNA Repair Pathways

Autor(es)

Osaki, Juliana H. ; Espinha, Gisele ; Magalhaes, Yuli T. ; Forti, Fabio L.

• Tipo de documento: Artigo Científico
• Fonte: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; v. 2016, p. 11-pg., 2016-01-01.

Resumo

Radiotherapy with gamma-radiation is widely used in cancer treatment to induce DNA damage reducing cell proliferation and to kill tumor cells. Although RhoA GTPase overexpression/hyperactivation is observed in many malignancies, the effect of RhoA activity modulation on cancer radiosensitivity has not been previously investigated. Here, we generated stable HeLa cell clones expressing either the dominant negative RhoA-N19 or the constitutively active RhoA-V14 and compared the responses of these cell lines with those of parental HeLa cells, after treatment with low doses of gamma-radiation. HeLa-RhoA-N19 and HeLa-RhoA-V14 clones displayed reduced proliferation and survival compared to parental cells after radiation and became arrested at cell cycle stages correlated with increased cellular senescence and apoptosis. Also, Chk1/Chk2 and histone H2A phosphorylation data, as well as comet assays, suggest that the levels of DNA damage and DNA repair activation and efficiency in HeLa cell lines are correlated with active RhoA. In agreement with these results, RhoA inhibition by C3 toxin expression drastically affected homologous recombination (HR) and nonhomologous end joining (NHEJ). These data suggest that modulation of RhoA GTPase activity impairs DNA damage repair, increasing HeLa cell radiosensitivity. (AU)

• Processo FAPESP: 11/05822-3 - Investigação da tirosina fosfatase VHR (DUSP3) na resposta a danos do DNA induzidas por radiação ultravioleta em células de melanoma humano
• Beneficiário: Alexsandro dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/18341-4 - Modulation of RhoA GTPase activity sensitizes human cervix carcinoma cells to gamma-radiation by attenuating DNA repair pathways
• Beneficiário: Fábio Luis Forti
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo
• Processo FAPESP: 08/58264-5 - Papel de GTPases da família Rho e de tirosina fosfatases duais no reparo de danos no DNA
• Beneficiário: Fábio Luis Forti
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores