Soy-derived isoflavones inhibit the growth of adult T-cell leukemia cells in vitro and in vivo.
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 G(1)/S or G(2)/M transition at 3 and 10 or 30 microM, respectively. Genistein upregulated p21 protein expression together with p53 accumulation. In addition, treatment with 30 microM 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 microM. However, marked phosphorylation of CHK2 and p53 could not be detected at 3 and 10 microM 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 gamma-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.
Yamasaki
Masao
M
Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, Japan.
Fujita
Satoshi
S
Ishiyama
Erina
E
Mukai
Ayako
A
Madhyastha
Harishkumar
H
Sakakibara
Yoichi
Y
Suiko
Masahito
M
Hatakeyama
Kinta
K
Nemoto
Takayuki
T
Morishita
Kazuhiro
K
Kataoka
Hiroaki
H
Tsubouchi
Hirohito
H
Nishiyama
Kazuo
K
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use*; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D013025:Glycine max; D014183:Transplantation, Heterologous
D007529:Isoflavones; C004742:daidzein; C086566:glycitein; D019833:Genistein