Icariin induces apoptosis in acute promyelocytic leukemia by targeting PIM1
Authors: Na Wei
Hong Zhang
Enze Li
Jiao Wang
Ping Li
Lin Wang
Luning Wang
Zhi Wang
Jing Li
Tongguo Song
Journal: Pharmacological Reports (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: APL; Icariin; JAK2; PIM1; STAT3
Affiliations: Qingdao University Affiliated Hospital, Qingdao, Shandong, China., Qingdao First Aid Center, Qingdao, Shandong, China., Qingdao University Affiliated Hospital, Qingdao, Shandong, China. Electronic address: .

Abstract:  Background: 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. Methods: 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. Results: 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. Conclusions: 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. 

Retracted: Yes

PubPeer comments:
 The author considered a group decision making problem with $m$ experts providing evaluation matrices $$P_1, R_2, cdots, P_m $$ The author then used an optimization model (Algorithm 1) to determine the weights of experts $$w_1, w_2,ldots, w_m$$ so that the aggregated evaluation matrix is $$P= w_1 P_1 + w_2 P_2 +cdots + w_m P_m$$ Since each evaluation matrix may not be close enough to the aggregated matrix, the author changed each original evaluation matrix with a convex combination with respect to the aggregated matrix as $$P _k = eta P_k + (1-eta)P$$ Such a procedure (Algorithm 2) is repeated, with the weights re-calculated by Algorithm 1, until all revised evaluation matrices are close enough to the aggregated matrix, which is iterated updated. However, during the whole procedure, the optimal weights determined by Algorithm 1 are always the same in all iterations and the aggregated matrix, although updated in very iteration, remains unchanged. The whole procedure returns its initial setting and is pointless.    , 
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 #2 Dear Prof. Zhao, If your argument stands, Theorem 1 would not hold.  Either your calculations are not correct or Theorem 1 in this paper does not hold. , 
 My calculations are correct, and Theorem 1 also holds. Please read them and the paper carefully! ,