Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10909556 | Leukemia Research | 2005 | 7 Pages |
Abstract
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.
Keywords
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromideFCSCMLPAMP-gpDNRFITCMDRYM529MTTNOD/SCIDP-glycoproteinPh+Ara-CZoledronic acidBisphosphonateApoptosisPeripheral bloodDaunorubicinRas proteinsZOLfetal calf serumcytarabinecombination indexphycoerythrinfluorescein isothiocyanateleukemiaAcute lymphoblastic leukaemiabone marrowMultidrug-resistantALLPamidronatePhiladelphia chromosome positivefraction affected
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Authors
Hidekazu Segawa, Shinya Kimura, Junya Kuroda, Kiyoshi Sato, Masaki Nogawa, Takeshi Yuasa, Asumi Yokota, Keiko Hodohara, Yoshihide Fujiyama, Taira Maekawa,