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

Abstract

Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer activity, immuno-enhancing effect and antimicrobial activity. However, other biological activities are unknown. Herein, we have shown that WSCO is able to inhibit proliferation of human leukemia HL-60 cells and induce these cells to differentiate. Treatment with WSCO for 4 days resulted in a concentration-dependent reduction in HL-60 cell growth as measured by cell counting and MTT assay. This effect was accompanied by a marked increase in the proportion of G(0)/G(1) cells as measured by flow cytometry. WSCO also induced differentiation of the cells as measured by phorbol ester-dependent reduction of NBT, morphological changes as examined by Wright-Giemsa staining and expression of CD11b but not of CD14 as analysed by flow cytometry, indicating differentiation of HL-60 cells toward granulocyte-like cells. A combination 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 agarose gel electrophoresis and quantitatively by Annexin V technique using flow cytometry. Collectively, there is a potential for WSCO in the treatment of myeloid leukemia.

• Authors: H O Pae, W G Seo, N Y Kim, G S Oh, G E Kim, Y H Kim, H J Kwak, Y G Yun, C D Jun, H T Chung
• Journal: Leukemia research (Leuk Res) Vol. 25 Issue 4 Pg. 339-46 (Apr 2001) ISSN: 0145-2126 [Print] England
• PMID: 11248331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• water soluble chitin
• Chitin
• Tretinoin
• Chitosan

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Differentiation (drug effects)
• Cell Division (drug effects)
• Chitin (analogs & derivatives, pharmacology)
• Chitosan
• Dose-Response Relationship, Drug
• Drug Synergism
• Granulocytes (cytology)
• HL-60 Cells (drug effects, pathology)
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, pathology)
• Tretinoin (pharmacology)