Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer

Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer activity, immune-enhancing effect and antimicrobial activity. However, oth er biological activities are unknown. Herein, we have shown that WSCO is ab le to inhibit proliferation of human leukemia HL-60 cells and induce these cells to differentiate. Treatment with WSCO for 4 days resulted in a concen tration-dependent reduction in HL-60 cell growth as measured by cell counti ng and MTT assay. This effect was accompanied by a marked increase in the p roportion of G(0)/G(1) cells as measured by flow cytometry. WSCO also induc ed differentiation of the cells as measured by phorbol ester-dependent redu ction of NET, morphological changes as examined by Wright-Giemsa staining a nd expression of CD11b but not of CD14 as analysed by flow cytometry, indic ating differentiation of HL-60 cells toward granulocyte-like cells. A combi nation of low dose of WSCO with all-trans retinoic acid, a differentiating agent toward granulocyte-like cells, exhibited a synergistic effect on the differentiation. In addition, treatment of HL-60 cells with WSCO for 6 or 8 days resulted in the induction of apoptosis as assayed qualitatively by ag arose gel electrophoresis and quantitatively by Annexin V technique using f low cytometry. Collectively, there is a potential for WSCO in the treatment of myeloid leukemia. (C) 2001 Elsevier Science Ltd. All rights reserved.