Abstract
(Purpose) Sulphoraphane (SFN) is an isothiocyanate derived from broccoli and other cruciferous vegetables. It has been reported that highly effective in antitumor by SFN inducing apoptosis and cell cycle arrest.
Our group has reported that the combination treatment of SFN and x-irradiation enhanced radiosensitivity. Our results demonstrated SFN led to radio-sensitization through the inhibition of DNA double strand breaks (DSBs) repair (NHEJ and HRR).
Here, we report that SFN enhanced radiosensitivity in human cancer cells exposure to high LET irradiation (carbon irradiation).
(Materials and methods) HeLa cells were used for this study. High LET radiation (carbon (290 MeV/n, 70 keV/um)) was used. HeLa cells treated with 20 uM SFN for 24 hours were irradiated. Cell survival level was monitored by colony forming assay. DNA DSB repair was measured by constant field gel-electrophoresis (CFGE) and immunofluorescence staining with gamma-H2AX (DSBs marker). We are also examining the possibility of activation of homologous recombination repair (HRR) pathway and non-homologous end joining (NHEJ) pathway using immunofluorescence staining experiments. We detected cell cycle distribution of cells treated with SFN and/or carbon irradiation by flow cytometry. We also monitored radiosensitivity by SFN in xenograft mouse model with HeLa cells.
(Results and discussion) In the cells treated with combination treatment of SFN and carbon irradiation, survival level was significantly reduced as compared with the control populations. In vivo study, the combined treatment with carbon irradiation (4 Gy) and SFN (i.p. 300 umol/kg, 8 times) showed an efficient inhibition tumor growth. Our results demonstrated that SFN enhancing radioresitivity of tumor therapy in vitro and in vivo.
