Antiproliferative Efficacy of the Third-Generation Bisphosphonate, Zoledronic Acid, Combined with Other Anticancer Drugs in Leukemic Cell Lines

  • Shinya Kimura
  • Junya Kuroda
  • Hidekazu Segawa
  • Kiyoshi Sato
  • Masaki Nogawa
  • Takeshi Yuasa
  • Oliver G. Ottmann
  • Taira Maekawa
Case Report

Abstract

Bisphosphonates are widely used to treat bone diseases and appear to possess antitumor activity. Moreover, we recently found that a third-generation bisphosphonate, zoledronic acid (ZOL), synergistically interacts with imatinib in vitro and in vivo to induce antileukemic activity, and others have reported that ZOL interacts synergistically with paclitaxel. Thus, the efficacy of other antileukemic agents combined with ZOL should be evaluated experimentally. In this study, we investigated the effects of concurrent and sequential combinations of ZOL with several commonly used antileukemic agents, including imatinib, on the in vitro growth of leukemia cell lines. As a complement to our previous finding that ZOL synergistically augments the effects of imatinib, we report here that ZOL acts additively when administered concurrently with hydroxyurea (HU), cytarabine (Ara-C), or daunorubicin (DNR) in some leukemic cell lines. Furthermore, one day of ZOL pretreatment augmented the sensitivity of imatinib and Ara-C. Therefore, concurrent or sequential administration of ZOL with imatinib, HU, Ara-C, or DNR may increase the efficacy of leukemia treatment.

Key words

Zoledronic acid Cytarabine Imatinib Leukemia Combination therapy 

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Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Shinya Kimura
    • 1
  • Junya Kuroda
    • 1
    • 2
  • Hidekazu Segawa
    • 1
    • 3
  • Kiyoshi Sato
    • 1
    • 4
  • Masaki Nogawa
    • 1
  • Takeshi Yuasa
    • 1
  • Oliver G. Ottmann
    • 5
  • Taira Maekawa
    • 1
  1. 1.Department of Transfusion Medicine and Cell TherapyKyoto University HospitalSakyo-ku, KyotoJapan
  2. 2.Department of Internal MedicineKyoto Prefectural University of MedicineKyoto
  3. 3.Department of Gastroenterology and HematologyShiga University of Medical ScienceOtsu
  4. 4.Department of Thoracic SurgeryFaculty of Medicine, Kyoto UniversityKyotoJapan
  5. 5.Department of HematologyJohann Wolfgang Goethe UniversityFrankfurtGermany

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