Activity of the morpholino anthracycline 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming units in vitro.
In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 micrograms/ml either for 1 hour (2-1 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19% in vitro response at 0.05 micrograms/ml and 69% at 0.5 micrograms/ml) than with 1-hour exposure (1.3% at 0.05 micrograms/ml and 12% at 0.5 micrograms/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 micrograms/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity with those tumors.
Ebrahim el-Zayat
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Dept. of Experimental Pathology, New York Medical College, Valhalla 10595, USA.
Izquierdo
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MA
Clark
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GM
Von Hoff
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002360:Carubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D015507:Drugs, Investigational / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000903:Antibiotics, Antineoplastic; D015507:Drugs, Investigational; C053537:morpholinoanthracycline MX2; D002360:Carubicin