Abstract | PURPOSE: This study evaluated the cytotoxic effects of imexon (NSC-714597) in tumor cells when combined with a broad panel of chemotherapeutic drugs. METHODS: The sulforhodamine B (SRB) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays were used to analyze the degree of growth inhibition for the combination studies in the A375 human malignant melanoma and RPMI 8226 human multiple myeloma cell lines, respectively. Cells were continuously exposed to both drugs at a constant molar ratio for 4-5 days. Combination effects were analyzed using the Median Effect method. Statistical significance was inferred if the 95% confidence interval for the combination interaction (C.I.) values for a particular two- drug combination did not include 1.0 (additivity). Synergy was inferred for C.I. values<1.0 and antagonism for CI values>1.0. RESULTS:
Imexon was synergistic when combined with DNA-binding agents ( cisplatin, dacarbazine, melphalan) and pyrimidine-based antimetabolites ( cytarabine, fluorouracil, gemcitabine) in both cell lines. Antagonistic combinations with imexon included methotrexate and the topoisomerase I ( TOPO I) and II ( TOPO II) inhibitors irinotecan, doxorubicin, mitoxantrone and etoposide. Docetaxel was synergistic with imexon in both cell lines whereas paclitaxel and fludarabine showed a mixed result. Dexamethasone and the proteasome inhibitor bortezomib showed synergy in myeloma cells and additivity in the melanoma cells. The vinca alkaloid, vinorelbine, and the multi-targeted antifol, pemetrexed, were additive with imexon in both cell lines. DISCUSSION:
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Authors | Julie Scott, Robert T Dorr, Betty Samulitis, Terry H Landowski |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 59
Issue 6
Pg. 749-57
(May 2007)
ISSN: 0344-5704 [Print] Germany |
PMID | 17333195
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Hexanones
- 4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
- Drug Screening Assays, Antitumor
- Hexanones
(administration & dosage, therapeutic use)
- Humans
- Melanoma
(drug therapy)
- Multiple Myeloma
(drug therapy)
- Tumor Cells, Cultured
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