In vitro effect on human leukemic K562 cells of co-administration of liposome-associated retinoids and cytosine arabinoside (Ara-C)

The administration of retinoids has been demonstrated to be of potential ut ility in the therapy of a wide spectrum of neoplastic pathologies due to th e ability to induce differentiation in a large variety of primary tumor cel ls as well as in vitro cultured cell lines. Moreover, a number of compounds , including hemin, cytosine arabinoside, and 5-aza-cytidine are able to ind uce erythroid differentiation of the erythroleukemic cell line K562. In thi s paper we determined whether a combined treatment of K562 cells with subop timal concentrations of cytosine arabinoside and retinoids containing lipos omes lead to a full expression of differentiated functions. Liposomes were prepared by reverse phase evaporation technique followed by extrusion throu gh polycarbonate filters. Cell growth kinetics studies and intracellular de tection of hemoglobin by benzidine staining were performed. The results obt ained showed that the combined treatment with liposomes containing retinoid s and sub-optimal concentration of ara-C is an effective strategy to induce K562 cell differentiation, minimizing at the same time toxic effects. Cont rol experiments aimed to determine possible selection of subpopulations of K562 cells suggest that the observed results are not related to toxicity an d/or potential selection of induced cells, In conclusion, liposomally deliv ered retinoids could be proposed for differentiation therapy as an effectiv e strategy in the treatment and management of malignancy, In addition, the finding that liposomally delivered retinoids increase the capacity of cytos ine arabinoside to induce erythroid differentiation, could be of interest i n studies aimed at the development of treatment able to reactivate fetal gl obin genes in beta-thalassemia patients. Am. J. Hematol, 62:33-43, 1999. (C ) 1999 Wiley-Liss, Inc.