9-Nitro-camptothecin delays growth of U-937 leukemia tumors in nude mice and is cytotoxic or cytostatic for human myelomonocytic leukemia lines in vitro.
The camptothecin derivatives 9-nitro-camptothecin (9NC) and 9-amino-camptothecin (9AC) inhibit similarly growth of HL-60, KG-1, and U-937 cells in vitro, whereas growth of THP-1 cells is inhibited by 9AC, but not by 9NC. Growth inhibition is accompanied by enlargement of cells which contain one (HL-60, THP-1) or more (KG-1, U-937) nuclei. Flow cytometry studies showed that 9NC-treated HL-60 and U-937 cells accumulate in the S and G2 phases of the cell cycle; then they die by apoptosis, with the HL-60 cells being more sensitive than U-937 cells to 9NC. In contrast, 9NC-treated KG-1 and THP-1 cells accumulate in S and G2 phases, but resist death by apoptosis. Of the cell lines tested, only U-937 cells xenografted in nude mice generated subcutaneous myeloid tumors, which exhibited a delayed growth in the presence of 9NC. Further, 9NC-treated advanced U-937 tumors regressed temporarily, indicating that U-937 cells consist of 9NC-sensitive and 9NC-resistant populations.
Pantazis
P
P
Stehlin Foundation for Cancer Research, Houston, Texas 77003.
Mendoza
J T
JT
Early
J A
JA
Kozielski
A J
AJ
Natelson
E A
EA
Giovanella
B C
BC
D000818:Animals; D000970:Antineoplastic Agents; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000188:drug therapy*; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; C079905:rubitecan; D002166:Camptothecin