Icariin induces apoptosis in acute promyelocytic leukemia by targeting PIM1.

Abstract

Acute promyelocytic leukemia (APL) is one type of acute myeloid leukemia (AML) featured by abnormal, heavily granulated promyelocytes. This study aimed to investigate the antitumor activity of icariin in APL cells. APL cell lines (HL-60 and NB4) were used to investigate the effect of icariin in vitro. Cell viability was determined by WST-8 proliferation assay, while cell apoptosis was assessed by flow cytometry. The mRNA and protein expression was determined by quantitative real-time polymerase chain reaction and Western blot, respectively. Moreover, small interfering RNA (siRNA) and overexpressing plasmid were used to manipulate the expression of PIM family kinase 1 (PIM1) to examine the role of PIM1 in icariin-induced apoptosis in APL cells. Icariin could significantly suppress cell growth and induce apoptosis in both model APL cell lines (HL-60 and NB4). It repressed the expression of PIM1 at the molecular level, which was responsible for the antitumor effect of icariin in APL cells. The ectopic overexpression of PIM1 significantly abrogated the inducing effect of icariin on apoptosis. In contrast, the knockdown of PIM1 by siRNA enhanced the antitumor effect of icariin in APL cells. Moreover, the findings indicated that icariin repressed the expression of PIM1 through generating reactive oxygen species and hence modulating the Janus kinase 2(JAK2)/Signal transducer and activator of transcription 3/5 (STAT3/5) signaling pathway. Icariin potently inhibits the cell growth of APL in vitro through inducing caspase-dependent apoptosis. Hence, it can be considered as a promising candidate therapeutic agent for treating APL, although further studies including clinical trials are warranted.