Effects of 4-hydroperoxy ifosfamide in combination with other anticancer agents on human cancer cell lines.
Ifosfamide is one of the currently available anticancer agents with a broad spectrum of clinical activity against a variety of tumors. To investigate its optimal combinations, we studied the effect of 4-hydroperoxy ifosfamide (the active form of ifosfamide) in combination with other anticancer agents against two human cancer cell lines, MG-63 (an osteosarcoma cell line) and MOLT-3 cells (a T-cell leukemia cell line). The cells were incubated for 4 days and 3 days, respectively, in the presence of 4-hydroperoxy ifosfamide and the other agent. Cell growth inhibition was determined by MTT assay. The effects of these drug combinations at the concentration producing 50% inhibition (IC50) were analyzed by the isobologram method. 4-Hydroperoxy ifosfamide showed additive effects with bleomycin, cisplatin, cytarabine, doxorubicin, etoposide, 5-fluorouracil, and mitomycin C, while it showed a protective effect with methotrexate in both cell lines. 4-Hydroperoxy ifosfamide showed an additive effect with vincristine in the MG-63 cell line, while it showed a sub-additive effect in the MOLT-3 cell line. No anticancer agents tested showed a supra-additive effect with 4-hydroperoxy ifosfamide. These data suggest that ifosfamide is advantageous for simultaneous administration with a majority of the anticancer agents we studied. Methotrexate is an inappropriate drug for simultaneous administration with ifosfamide.
Yazawa
Y
Y
Division of Orthopedic Oncology, Tochigi Cancer Center, 4-9-13 Younan, Utsunomiya, Tochigi 320-0834, Japan.
Takagi
T
T
Asakura
S
S
Suzuki
K
K
Kano
Y
Y
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; C012353:hydroperoxyisophosphamide; D007069:Ifosfamide