Chemopreventive Agent Sulforaphane Enhances Radiosensitivity in Human Tumor Cells
Chemopreventive agent sulforaphane enhances radiosensitivity in human tumor cells.
Int J Cancer. 2009 Sep 1;125(5):1205-11.
Yu D, Sekine-Suzuki E, Xue L, Fujimori A, Kubota N, Okayasu R.
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Inage-ku, Chiba-shi, Japan.
Sulforaphane (SFN), an isothiocyanate derived from broccoli and other cruciferous vegetables, is a positive regulator of phase II detoxification enzymes andis highly effective in protection against chemically induced cancers by inducing apoptosis and cell cycle arrest. Here, we report that SFN also enhances radiosensitivity in human tumor cells. Cell survival in HeLa human cervix carcinoma cells pretreated with SFN was significantly lower than in cells treated with radiation only. Constant-field gel electrophoresis and a gamma-H2AX foci assay showed marked inhibition of DSB repair in irradiated cells treated with SFN, while little inhibition was observed in cells with DMSO (control). In addition, immunofluorescence experiments revealed a significant delay in Rad51 (a key protein for homologous recombination repair) foci formation and disappearance in irradiated cells treated with SFN when compared to the cells with X-irradiation alone. The dephosphorylation of DNA-PKcs (a critical nonhomologous end joining protein) was also markedly delayed by SFN pretreatment in irradiated cells. These DSB repair inhibition data partially support the high apoptotic frequency of irradiated cells pretreated with SFN. Furthermore, the combined treatment of X-rays and SFN (i.p. 300 micromol/kg) in the xenograft model with HeLa cells showed efficient inhibition of in vivo tumor growth. To the best of our knowledge, our study is the first report showing sulforaphane -enhanced radiosensitivity of tumor cells in vitro and in vivo, which opens the door for a multitude of clinical applications for chemoradiotherapy using Sulforaphane.
Note from ISS: Several crucifer sprouts including broccoli sprouts are currently the most potent natural source of sulforaphane known. They often produce 10 to 100 times the amount of sulforaphane as their corresponding mature vegetables.
“Broccoli sprouts have a very high concentration of sulforaphane since this compound originates in the seed and is not made in the plant as it grows. One sprout contains all of the sulforaphane that is present in a full grown broccoli plant.” “Nutrition and cancer: a review of the evidence for an anti-cancer diet”Nutr J. 2004 Oct 20;3:19, Donaldson MS. Hallelujah Acres Foundation, 13553 Vantage Hwy, Ellensburg, WA 98926, USA.