In-vitro toxicity of Ukrain against human Ewing tumor cell lines.
Ukrain is advertised by the manufacturer as a drug for alternative cancer cures with high activity against progressive Ewing tumors. Using the MTT assay, we compared the cytotoxicity of Ukrain with the cytotoxicity of N,N',N''-triethylenethiophosphoramide (thioTEPA), Chelidonium majus L. alkaloids, doxorubicin, cyclophosphamide and etoposide against four human Ewing tumor cell lines. In addition, we studied the cytotoxicity of thioTEPA combined with C. majus L. alkaloids after 48, 72 and 96 h. All compounds reduced the growth of Ewing tumor cell lines in a dose-dependent manner. The concentrations that reduced cell growth by 50% ranged between 6.2 and 31.1 micromol/l for Ukrain, 1.9 and 26.1 micromol/l for C. majus L. extract, and 1.7 and 448 micromol/l for thioTEPA. The sensitivity profile of Ukrain was comparable to that of the C. majus L. alkaloids, and different from that of thioTEPA, cyclophosphamide, etoposide and doxorubicin. Overall, doxorubicin was the most cytotoxic drug followed by cyclophosphamide. Ukrain and the C. majus L. alkaloids were slightly more cytotoxic than etoposide, while thioTEPA showed the lowest cytotoxicity. Co-exposure of thioTEPA with C. majus L. alkaloids resulted in additive but not in synergistic cytotoxicity. The in-vitro results indicate that the cytotoxicity of Ukrain against Ewing tumors is comparable to that of etoposide. While the latter can be used on the basis of broad clinical experience and known risk-benefit ratio, Ukrain for the present might be considered as a candidate for subsequent drug development by xenograft studies followed by systematic clinical trials.
Lanvers-Kaminsky
Claudia
C
Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany.
Nolting
Dorothea-Maria
DM
Köster
Julia
J
Schröder
Anke
A
Sandkötter
Julia
J
Boos
Joachim
J
D001600:Berberine Alkaloids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D028281:Chelidonium; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D010617:Phenanthridines / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000473:pathology; D013852:Thiotepa / Q000494:pharmacology
D001600:Berberine Alkaloids; D010617:Phenanthridines; D010936:Plant Extracts; C060921:ukrain; D004317:Doxorubicin; D013852:Thiotepa