Antiproliferative efficacy of the third-generation bisphosphonate, zoledronic acid, combined with other anticancer drugs in leukemic cell lines.
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.
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan. shkimu@kuhp.kyoto-u.ac.jp
Shinya
S
Kimura
Junya
J
Kuroda
Hidekazu
H
Segawa
Kiyoshi
K
Sato
Masaki
M
Nogawa
Takeshi
T
Yuasa
Oliver G
OG
Ottmann
Taira
T
Maekawa
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D000068877:Imatinib Mesylate; D007093:Imidazoles / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D001549:Benzamides; D004164:Diphosphonates; D007093:Imidazoles; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D014750:Vincristine; D000077211:Zoledronic Acid; D000068877:Imatinib Mesylate; D006918:Hydroxyurea; D008727:Methotrexate; D003630:Daunorubicin