Physcion 8-O-β-glucopyranoside exhibits anti-leukemic activity through targeting sphingolipid rheostat
Authors: Ping Zhao
Fengxue Wang
Zengmin Wang
Jinyan Han
Lei Sheng
Weiqin Shao
Journal: Pharmacological Reports (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Acute lymphoblastic leukemia; Apoptosis; Physcion 8-O-β-glucopyranoside; Sphingosine kinase 1.

Abstract:  Background: Acute lymphoblastic leukemia (ALL) is the most common fatal cancer in people younger than 20 years of age. This study was designed to explore the anti-leukemia activity of physcion 8-O-β-glucopyranoside (PG) in B-cell ALL. Methods: NALM6 and SupB15 cells were used as model cell lines. Cell viability, cell apoptosis, cell cycle distribution were determined by CCK-8 assay, DNA fragmentation assay and flow cytometry, and flow cytometry, respectively. Expression of proteins involved in cell apoptosis and cell cycle regulation was determined by western blot and the levels of ceramide and sphingosine 1-phosphate (S1P) were determined by ELISA. Activity of sphingosine kinase 1 (SphK1) was also determined with a Sphingosine Kinase Assay Kit. In the present study, both model cell lines were transfected with siRNA targeting SphK1 or an overexpression plasmid to examine the role of SphK1 in the anti-leukemia activity of PG. Moreover, the efficacy of PG was examined in vivo in a mouse model by measuring survival and spleen weight. Results: Our results provided experimental evidence that PG could significantly induce apoptosis and cell cycle arrest in vitro. Mechanistically, the anti-leukemia activity of PG was mediated by its ability to repress SphK1 and thus modulate ceramide-S1P rheostat. Moreover, the anti-leukemia activity of PG was also verified in a murine model. Conclusion: Collectively, our results indicate that PG may be a promising agent for the treatment of B-cell leukemia. 

Retracted: Yes

PubPeer comments:
 Above: Fig 6C. Below: Fig 1C from [Wang et al (2017)] . ![file] Unexpected similarities between FACS plots, despite different conditions and different cell lines. , 
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 Retracted [6 November 2020] . ------------------------------------ The Editor in Chief has retracted this original article because of concerns regarding a number of figures presented in this work, which question the integrity of the data. Specifically, unexpected similarities have been found between plots presented in Figs. 4c and 5c and those published elsewhere with different labels: Fig. 1c in [1], Fig. 4b in [2] and Fig. 7b in ([3], retracted). The authors were unable to provide raw data. Author Lei Sheng agreed to retraction but has not stated if they agree to this retraction notice. The editor was not able to obtain a current email address for the remaining authors. References - [1] Wang Q, et al. Physcion 8-O-u03b2-glucopyranoside suppresses tumor growth of hepatocellular carcinoma by downregulating PIM1. Biomed Pharmacother. 2017;92:451u20138. https: doi.org 10.1016 j.biopha.2017.05.110 - [2] Yang X, et al. Physcion 8-O-u03b2-glucopyranoside alleviates oxidized low-density lipoprotein-induced human umbilical vein endothelial cell injury by inducing autophagy through AMPK SIRT1 signaling. J Cardiovasc Pharmacol. 2019;74(1):53u201361. https: doi.org 10.1097 FJC.0000000000000680 - [3] Liu K, et al. Hispidulin suppresses cell growth and metastasis by targeting PIM1 through JAK2 STAT3 signaling in colorectal cancer. Cancer Sci. 2018;109(5):1369u201381. https: doi.org 10.1111 cas.13575 , 
 [Source: Jining First People s Hospital Release time: 2021-12-17] : In order to strengthen the construction of scientific research integrity, severely punish violations, and create a good environment for scientific and technological innovation, the relevant paper issues recently investigated and dealt with by this unit are hereby notified as follows. 9. The paper  Physcion 8-O-u03b2-glucopyranoside exhibits anti-leukemic activity through targeting sphingolipid rheostat published by Sheng Lei of our hospital as the corresponding author and Han Jinyan of Shandong Provincial Hospital as the first author has been found to have falsified data, Academic misconduct by fabricating the research process and inappropriate authorship. Our hospital will deal with the relevant responsible persons as follows: Sheng Lei (corresponding author): cancel the application qualifications for scientific research projects, scientific research awards, scientific and technological achievements, scientific and technological talent plans within 5 years; cancel the nomination or recommender, nominee or recommender for 5 years , evaluation experts and other qualifications; cancel their membership or membership in academic institutions such as societies and associations; recover the author s personal research awards and honorary titles; postpone promotion to a higher-level professional and technical position for one year; instruct as soon as possible Contact the magazine for retraction; party warning. Shandong Provincial Hospital dealt with the relevant responsible persons as follows: Han Jinyan (first author): cancel the qualification to apply for or apply for science and technology plan projects within 5 years; cancel the qualifications as a nominee or recommender, nominee or recommender, and review expert within 5 years. Research integrity exhortation talk; public criticism; cancel this year s first evaluation, and the annual assessment shall not be determined as excellent; withdraw the profit from the use of this article; withdraw the qualification of deputy chief nurse. Zhao Ping, Wang Zengmin, Shao Weiqin, and Wang Fengxue (participating authors): A talk on scientific research integrity admonitions. ,