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

Author(s)

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

• Document type: Journal article
• Source: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; v. 2016, p. 11-pg., 2016-01-01.

Abstract

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)

• FAPESP's process: 11/05822-3 - Investigation of VHR (DUSP3) protein tyrosine phosphatase in DNA damage response induced by ultraviolet light in human melanoma cell lines
• Grantee: Alexsandro dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/18341-4 - Modulation of RhoA GTPase activity sensitizes human cervix carcinoma cells to gamma-radiation by attenuating DNA repair pathways
• Grantee: Fábio Luis Forti
• Support Opportunities: Regular Research Grants - Publications - Scientific article