@misc{oai:repo.qst.go.jp:00069326, author = {Sekine, Emiko and Yu, Dong and Fujimori, Akira and Anzai, Kazunori and Kubota, Nobuo and Okayasu, Ryuichi and 関根 絵美子 and 于 冬 and 藤森 亮 and 安西 和紀 and 窪田 宜夫 and 岡安 隆一}, month = {Apr}, note = {Sulforaphane (SFN), an isothiocyanate isolated from broccoli, has been recognized mainly as a preventive agent for human cancers. Several reports also indicated that SFN suppressed proliferation of cancer cells by cell cycle arrest and by inducing apoptosis through activation of the caspase apoptosis pathway. DNA double-strand breaks (DSBs) are thought to be the most important lesions produced in cells exposed to toxic agents such as ionizing radiation (IR). Here, we present a new discovery that the biological effects exerted by SFN might be a consequence of DNA DSBs it produces. HeLa cells were exposed to various concentrations of SFN and several biological end points were studied. The cell growth was measured for several days and the induction of DNA DSB was examined using constant field gel electrophoresis (CFGE) as well as gamma-H2AX assay. Our data revealed that the cell growth was impaired in a SFN dose dependent manner, and DNA DSBs were also induced in a drug dose and treatment time dependent manner. For example, after 20microM SFN treatment for 24 hours, a significant number of DNA DSBs was induced in HeLa cells. Moreover, our immuno-staining experiments indicated the appearance of Rad51 (an essential protein associated with homologous recombination repair (HRR)) foci observed in a dose and time dependent manner along with DNA DSB production. In contrast, there was no phosphorylation of DNA-PKcs (a critical non-homologous end joining (NHEJ) protein) observed in cells exposed to SFN, suggesting that DSBs caused by SFN might be cell cycle dependent. In summary our data clearly demonstrate the induction of DNA DSBs by SFN, and these might be repaired by HRR pathway. Our results suggest that SFN could be used as an effective anticancer agent in addition to its well-recognized chemo-preventive property., AACR Annual Meeting 2008}, title = {Sulforaphane exerts its biological effects by introducing DNA double strand breaks}, year = {2008} }