Differentiation of HL-60 myeloid leukemia cells induced by all-trans retinoic acid is enhanced in combination with caffeic acid.
We investigated a possible enhancement of all-trans retinoic acid (ATRA)-induced differentiation of HL-60 human myeloid leukemia cells by caffeic acid (CA), a widely distributed plant phenolic compound. Our results showed that CA, in the concentration of 13 or 52 micro M, had no or minimal influence on cell differentiation, whereas the differentiating activity of ATRA was potentiated by CA treatment. We proved, using flow cytometric detection of the CD66b surface molecule, a synergistic effect of CA: at day 10, 18.3% of CD66b-positive cells were detected after treatment with ATRA only, and 33% when CA and ATRA were combined together. NBT-assay confirmed that this additive effect of CA on ATRA-induced differentiation. Proliferating activity as assessed by MTT-assay was generally not affected by CA at given concentrations. However, cell proliferation was significantly reduced by 52 micro M CA at 96-h intervals. This effect was markedly enhanced when CA, at both concentrations, and ATRA were combined. The possibility to enhance the differentiation potential of ATRA by CA may improve outcomes in the therapy of acute promyelocytic leukemia.
Veselská
Renata
R
Department of Biology, Medical Faculty, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic. rvesel@med.muni.cz
Zitterbart
Karel
K
Auer
Jan
J
Neradil
Jakub
J
D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002109:Caffeic Acids / Q000008:administration & dosage* / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D049109:Cell Proliferation; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D018922:HL-60 Cells; D006801:Humans; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D008956:Models, Chemical; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504120:CEACAM8 protein, human; D002109:Caffeic Acids; D015815:Cell Adhesion Molecules; D004396:Coloring Agents; D058851:GPI-Linked Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014212:Tretinoin; C022616:thiazolyl blue; C040048:caffeic acid