Abstract
Sulphoraphane (SFN), an isothiocyanate devrived from broccoli and other cruciferous vegetables, is a positive regulator of Phase II detoxification enzymes. It is highly effective in affording protection against chemically induced cancers by inducing apoptosis and cell cycle arrest. Here, we report that SFN enhanced radiosensitivity in HeLa human cervix epithelium carcinoma cells by inhibiting double strand breaks (DSBs) repair pathways. HeLa cells stimulated with SFN for 24 hours were irradiated, and cell survival level was significantly reduced as compared with the control populations. DNA double strand breaks (DSBs) repair as measured by constant field gel-electrophoresis showed a clear inhibition of DSBs repair in cells with SFN, while little inhibition was observed in cells with negative control. Our immunofluorescence staining experiments revealed a significant delay in gamma H2AX (DSBs marker), Rad51 (homologous recombination repair (HRR) related protein) and phosphorylation of DNA-PKcs (a critical non-homologous end joining (NHEJ) protein) foci formation in cells with SFN when compared with the control populations. In addition, the combined treatment with radiation and SFN (i.p. 300umol/kg, 1 time/day) in xenograft model with HeLa cells showed an efficient inhibition in vivo tumor growth. Our results demonstrated SFN led to radio-sensitization through the inhibition of DSBs repair; a possibility of using SFN as an effective radiosensitizer in tumor radiotherapy may arise. To the best of our knowledge, the present study is the first published report about SFN enhancing radioresitivity of tumor therapy in vitro and in vivo.
