WATER-SOLUBLE CHITOSAN SENSITIZES APOPTOSIS IN HUMAN LEUKEMIA CELLS VIA THE DOWNREGULATION OF BCL-2 AND DEPHOSPHORYLATION OF AKT

Chitosan, a natural polysaccharide, has been reported to possess biologically beneficial properties, including antitumor, anti-inflammatory, antimicrobial and immune-enhancing effects. However, the precise molecular mechanism of the anticancer activity of chitosan is poorly understood. In this study, we investigated whether water-soluble chitosan (WSC) has pro-apoptotic activity on the human leukemia cells (U937, K562, HL60 and THP-1). Our results showed that treatment with WSC for 24h inhibited cell proliferation and induced apoptosis in leukemic cells via the mitochondria-dependent pathway. This effect was accompanied by a marked increase in caspase activation and the cleavage of poly(ADP-ribose) polymerase. In addition, WSC decreased Bcl-2 expression in all leukemic cells and reversed the ectopic expression of Bcl-2 in U937 cells. WSC also suppressed the phosphorylation of Akt, thereby inhibiting cell proliferation. Taken together, these data suggest that WSC inhibits proliferation and induces apoptosis in leukemia cells through the suppression of Bcl-2- and the Akt-dependent signaling pathways. PRACTICAL APPLICATIONS Chitosan is a linear polysaccharide obtained from deacetylated chitin. Usage of this compound is significantly increasing because of its immunomodulating, anticancerous, antibacterial and antiviral activity. However, application of chitosan is limited because chitosan is a weak base and is insoluble in water and organic solvent. Water-soluble chitosan (WSC) is allowed to be used for more convenient administration and might provide new strategy to prevent cancer growth. These attempts give possibilities for the applications of WSC in economic markets.