Effects of anthracycline derivatives on human leukemia K562 cell growth and differentiation.
New derivatives of daunorubicin (DRB), doxorubicin (DOX), and epidoxorubicin (EDOX) with an amidine group bonded to C-3' of daunosamine moiety with either morpholine or hexamethyleneimine ring attached to the amidine group are studied in this paper. We have shown that all of these newly synthesized anthracycline derivatives inhibit human leukemia K562 cell line proliferation but only some of them induce erythroid differentiation when used at subtoxic concentrations. Morpholine derivative of DOX has the greatest potential to inhibit proliferation and to induce differentiation in vitro. The correlation between these two cellular processes was also significant for other tested compounds. In cell cycle analysis, we have demonstrated that those anthracycline derivatives that exert the greatest cytostatic potential caused G(2)/M arrest, which in turn, might contribute to the development of a differentiating phenotype. The concentrations of the compounds used in the study are pharmacologically relevant. These new potent inducers of differentiation might be exploited as anticancer drugs for treatment of leukemia by differentiation therapy.
Czyz
Malgorzata
M
Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland. mczyz@csk.umed.lodz.pl
Szulawska
Agata
A
Bednarek
Andrzej K
AK
Düchler
Markus
M
D018943:Anthracyclines / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D019394:Ki-67 Antigen / Q000187:drug effects / Q000235:genetics; D020527:Microscopy, Scanning Probe / Q000379:methods; D009025:Morpholines / Q000737:chemistry / Q000633:toxicity
D018943:Anthracyclines; D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D009025:Morpholines