West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 14 11 2013 11 01 Senescence Effects of Angelica sinensis Polysaccharides on Human Acute Myelogenous Leukemia Stem and Progenitor Cells 6549 6556 28331 EN Journal Article 1970 01 01 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. https://journal.waocp.org/article_28331_fbc567dcf31462b7263c292bd501ffc8.pdf