Pae H O, Seo W G, Kim N Y, Oh G S, Kim G E, Kim Y H, Kwak H J, Yun Y G, Jun C D, Chung H T
Department of Microbiology and Immunology, Wonkwang University School of Medicine, 570-749, Chonbuk, South Korea.
Leuk Res. 2001 Apr;25(4):339-46. doi: 10.1016/s0145-2126(00)00138-7.
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.
据报道，水溶性壳聚糖寡聚物（WSCO）具有抗癌活性、免疫增强作用和抗菌活性。然而，其其他生物学活性尚不清楚。在此，我们表明WSCO能够抑制人白血病HL-60细胞的增殖并诱导这些细胞分化。用WSCO处理4天导致通过细胞计数和MTT测定法测量的HL-60细胞生长呈浓度依赖性降低。通过流式细胞术测量，这种作用伴随着G(0)/G(1)期细胞比例的显著增加。WSCO还通过佛波酯依赖性的NBT还原、瑞氏-吉姆萨染色检查的形态学变化以及流式细胞术分析的CD11b而非CD14的表达来诱导细胞分化，表明HL-60细胞向粒细胞样细胞分化。低剂量的WSCO与全反式维甲酸（一种向粒细胞样细胞的分化剂）联合使用，对分化表现出协同作用。此外，用WSCO处理HL-60细胞6天或8天导致通过琼脂糖凝胶电泳定性测定和使用流式细胞术的膜联蛋白V技术定量测定诱导凋亡。总体而言，WSCO在治疗髓系白血病方面具有潜力。
