aclarubicin and Cell-Transformation--Neoplastic

Topics: Aclarubicin; Acute Disease; Alkylating Agents; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cell Transformation, Neoplastic; DNA; Leukemia; Naphthacenes; Purine Nucleotides; Pyrimidine Nucleotides

Anthracycline antitumor drugs induce erythroid differentiation of the K562 erythroleukemic cell line at subtoxic concentrations. Aclacinomycin (ACM) stimulates this process by activating the erythroid transcription factor GATA-1, that controls genes involved in hemoglobin biosynthesis. To investigate the implication of GATA-1 in this process, we used a specific anti-GATA-1 polyclonal antibody that we produced in our laboratory. The GATA-1 transcription factor was then monitored during erythroid differentiation induced by aclacinomycin. Here we show that a cellular redistribution and a modification of the phosphorylation state of this transcription factor occurred during ACM-mediated cell differentiation. It suggests that anthracyclines can induce the erythroid differentiation of neoplastic cells by activating the transcription factor GATA-1, probably via its clustering into nuclear foci.

Topics: Aclarubicin; Adjuvants, Immunologic; Antibody Specificity; Cell Compartmentation; Cell Nucleus; Cell Transformation, Neoplastic; DNA-Binding Proteins; Dose-Response Relationship, Drug; Erythrocytes; Erythroid Precursor Cells; Erythroid-Specific DNA-Binding Factors; Erythropoiesis; GATA1 Transcription Factor; Gene Expression Regulation, Leukemic; Hemoglobins; Humans; K562 Cells; Leukemia; Microscopy, Confocal; Phosphoric Monoester Hydrolases; Phosphorylation; Transcription Factors

The growth fraction of cancer cells, estimated by the monoclonal antibody Ki-67 labelling, and DNA content were determined simultaneously en K562 human leukemic cells by flow cytometry. Adriamycin, aclacinomycin A and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreases the fraction of Ki-67 positive cells, Ki-67 negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Topics: Aclarubicin; Alkaloids; Antibodies, Monoclonal; Antineoplastic Agents; Benzophenanthridines; Cell Transformation, Neoplastic; DNA; Doxorubicin; Flow Cytometry; Humans; Leukemia; Phenanthridines

Effects of aclacinomycin-A (ACM) on leukemic cells and normal hematopoietic stem cells were studied for the purpose of evaluating the usefulness of this agent as an antileukemic agent. ACM suppressed not only leukemic colony-forming unit (LCFU) in the radiation-induced murine erythroleukemia, but also normal hematopoietic stem cells (CFU-S, CFU-C) in mice. However, LCFU was the most sensitive to ACM. After the administration of ACM at a dose of 5 mg/kg. LCFU was suppressed to 0.02 of the control on day 3 and recovered within 5 days. Splenic CFU-S and CFU-C were suppressed to the nadirs on day 2 and day 1, respectively, and they recovered within 5 days. On the basis of the differences in the sensitivities to ACM and recovery patterns between LCFU and normal hematopoietic stem cells. ACM at a single dose of 5 mg/kg was administered every 3 days (total dose of 25 mg/kg) into leukemic mice, and the increase in mean lifespan obtained 113.9%. Effectiveness of ACM in the treatment of acute leukemia was discussed.

Topics: Aclarubicin; Animals; Bone Marrow Cells; Cell Survival; Cell Transformation, Neoplastic; Colony-Forming Units Assay; Female; Hematopoietic Stem Cells; Leukemia, Experimental; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Naphthacenes; Neoplasm Transplantation; Spleen

Topics: Aclarubicin; Adult; Animals; Cell Transformation, Neoplastic; Colony-Forming Units Assay; Hematopoietic Stem Cells; Humans; Leukemia, Experimental; Leukemia, Myeloid, Acute; Mice; Mice, Inbred Strains; Naphthacenes