Open AccessTopoisomerase Inhibitors Have Potent Differentiation‐inducing Activity for Human and Mouse Myeloid Leukemia Cells
Author(s) -
Nakaya Kazuyasu,
Chou Sawako,
Kaneko Motohisa,
Nakamura Yasuharu
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb01827.x
Subject(s) - camptothecin , hl60 , topoisomerase , cellular differentiation , biology , k562 cells , u937 cell , leukemia , cell culture , amsacrine , myeloid leukemia , microbiology and biotechnology , myeloid , cancer research , biochemistry , dna , immunology , genetics , gene
DNA topoisomerase inhibitors, camptothecin and 4′‐demethylepipodophyllotoxin ethylidene‐jS‐D‐glucoside (VP16) had strong differentiation‐inducing activity for all five kinds of leukemia cells examined (human HL60, U937, ML1, and K562 cells and mouse Ml cells) as judged from measurements of various differentiation markers. The characteristics that appeared as a result of differentiation induced by these inhibitors were essentially similar in every cell line. Exposure to VP16 for 2 h induced both differentiation and DNA‐strand breaks in K562 cells, whereas podophyl‐lotoxin, which lacks topoisomerase II inhibitory activity, induced neither differentiation nor DNA‐strand breaks in these cells. These results suggest a parallelism between the induction of differentiation and that of DNA‐strand breaks. The combination of VP16 and recomhinant tumor necrosis factor α (rTNFα) synergistically induced differentiation of human U937, ML1, and M1 cells and had an additive effect on HL60 cells. Simultaneous treatment with rTNFa plus camptothecin or VP16, or pretreatment with camptothecin or VP16, followed by rTNFα induced marked differentiation of Ml cells. These results indicate that inhibition of topoisomerase (either topoisomerase I or II) followed by the action of rTNFα was effective in inducing differentiation of leukemia cells.