Soy‐derived isoflavones inhibit the growth of adult T‐cell leukemia cells in vitro and in vivo

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Abstract
Adult T‐cell leukemia occurs in human T‐lymphotropic virus type I‐infected individuals and is endemic to the south‐western area of Kyushu in Japan. In this communication, we examined the effect of soy isoflavones on the growth of adult T‐cell leukemia cells in vitro and in vivo. In the in vitro study, daidzein and genistein but not glycitein significantly inhibited the proliferation of ED‐40515 and Hut102 cells in a dose‐dependent manner. Among the isoflavones studied, genistein had the highest growth‐inhibitory effect; however, genistein did not exert an apparent growth‐inhibitory effect on Jurkat and Molt‐4 cells, which were non‐adult T‐cell leukemia cells. Genistein prevented the G1/S or G2/M transition at 3 and 10 or 30 µM, respectively. Genistein upregulated p21 protein expression together with p53 accumulation. In addition, treatment with 30 µM genistein strongly induced phosphorylation of checkpoint kinase (CHK) 2 and p53 at serines 15, 20 and 37. Caffeine, an inhibitor of ataxia‐telangiectasia mutated protein kinase, alleviated the genistein‐induced p53 and CHK2 phosphorylation, suggesting the involvement of DNA damage at 30 µM. However, marked phosphorylation of CHK2 and p53 could not be detected at 3 and 10 µM genistein. These data indicate that genistein has biphasic growth‐inhibitory properties. The in vivo studies demonstrated that soy‐derived isoflavones significantly inhibit ED‐40515 cell growth and infiltration into various organs in non‐obese diabetic severe combined‐immunodeficiency common γ‐chain knockout mice. Taken together, it is evident that soy isoflavones might serve as a promising compound for the treatment of adult T‐cell leukemia. (Cancer Sci 2007; 98: 1740–1746)

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