Abstract
Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro- megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/ STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.
Highlights
Leukemia is a clonal disorder that results as a consequence of an acquired somatic mutation in hematopoietic progenitor cells that block normal differentiation and cell death that confer a proliferative growth advantage
We focus on the effect of Angelica sinensis polysaccharide (ASP) on both Janus kinas 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) activation and EPO-mediated JAK2/STAT5 activation in K562 cells to determine the underlying mechanism by which ASP preferentially induces erythroid differentiation of K562 cells
Thereafter, K562 cells cytospun onto slides, air-dried, fixed with ice-cold were subjected to the safe optimal ASP concentration methanol for 15min
Summary
Leukemia is a clonal disorder that results as a consequence of an acquired somatic mutation in hematopoietic progenitor cells that block normal differentiation and cell death that confer a proliferative growth advantage. Primary strategies for leukemia therapeutics were focused on DNA damages of cancer cells with radiation or chemical drugs. Remission can be achieved in most patients, relapse is common and long-term survival is poor for most cases, as well as the unavoidable toxicities to local norm tissues. Based on this awkward situation, an alternative strategy of inducing differentiation which consists in reprograming malignant cells to undergo terminal differentiation instead of killing them through cytotoxicity has so far gained a great interest (Tsiftsoglou et al, 2009; Sexauer et al, 2012). Accumulating studies have provided convincing evidences that human leukemia can be induced differentiation with some natural compounds, traditional Chinese drugs or main ingredients (Wu and Xie, 2008; Hsu et al, 2009; Zhao et al, 2012;)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call