The anti-leukemic efficacy of the third generation bisphosphonate ONO5920/YM529.
Ras proteins are frequently over-expressed in leukemia and contribute to leukemogenesis. We evaluated the anti-leukemic efficacy of a new third-generation bisphosphonate, ONO5920/YM529 (YM529). YM529 prevents the prenylation of Ras proteins and inhibited the growth of leukemic cells including a P-glycoprotein (P-gp) over-expressing cell line in a concentration- and time-dependent manner by inducing apoptosis in vitro. Moreover, YM529 synergistically augmented the anti-leukemic activities of paclitaxel and daunorubicin in vitro. Importantly, YM529 prolonged the survival of NOD/SCID mice engrafted with human primary leukemic cells. These findings indicate that the YM529 may become a novel molecular therapeutic class for treatment of leukemias.
Segawa
Hidekazu
H
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
Kimura
Shinya
S
Kuroda
Junya
J
Sato
Kiyoshi
K
Nogawa
Masaki
M
Yuasa
Takeshi
T
Yokota
Asumi
A
Hodohara
Keiko
K
Fujiyama
Yoshihide
Y
Maekawa
Taira
T
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000633:toxicity*; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D017368:Protein Prenylation / Q000187:drug effects; D014183:Transplantation, Heterologous; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529; D018631:ras Proteins