Senescence Effects of Angelica sinensis Polysaccharides on Human Acute Myelogenous Leukemia Stem and Progenitor Cells

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thusrepresent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeuticstrategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelicasinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectivelyinhibited human AML CD34+CD38− cell proliferation in vitro culture in a dose-dependent manner while sparingnormal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASPexerted cytotoxic effects on AML K562 cells, especially LSC-enriched CD34+CD38− cells. Colony formation assaysfurther showed that ASP significantly suppressed the formation of colonies derived from AML CD34+CD38−cells but not those from normal CD34+CD38− cells. Examination of the underlying mechanisms revealed thatASP induced CD34+CD38− cell senescence, which was strongly associated with a series of characteristic events,including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16,P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of thesefindings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.