TY - JOUR
T1 - 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
AU - Pantazis, P.
AU - Mendoza, J. T.
AU - Early, J. A.
AU - Kozielski, A. J.
AU - Natelson, E. A.
AU - Giovanella, B. C.
PY - 1993/2
Y1 - 1993/2
N2 - 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.
AB - 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.
KW - cell cycle
KW - leukemia tumors
KW - myeloid cells
KW - nude mouse
UR - http://www.scopus.com/inward/record.url?scp=0027399619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027399619&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0609.1993.tb00146.x
DO - 10.1111/j.1600-0609.1993.tb00146.x
M3 - Article
C2 - 8440362
AN - SCOPUS:0027399619
SN - 0902-4441
VL - 50
SP - 81
EP - 89
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 2
ER -