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, 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.
Department of Microbiology and Immunology, Wonkwang University School of Medicine, 570-749, Chonbuk, South Korea.
H O
HO
Pae
W G
WG
Seo
N Y
NY
Kim
G S
GS
Oh
G E
GE
Kim
Y H
YH
Kim
H J
HJ
Kwak
Y G
YG
Yun
C D
CD
Jun
H T
HT
Chung
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology*; D048271:Chitosan; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006098:Granulocytes / Q000166:cytology*; D018922:HL-60 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; C400945:water soluble chitin; D002686:Chitin; D014212:Tretinoin; D048271:Chitosan