Retracted : Euxanthone inhibits glycolysis and triggers mitochondria‐mediated apoptosis by targeting hexokinase 2 in epithelial ovarian cancer
Authors: Jun Zou
Yamei Wang
Mingdi Liu
Qian Gao
Wenjian Zheng
Haijing Wang
Xiushu Huang
Journal: Cell Biochemistry and Function (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HK2; STAT3; apoptosis; epithelial ovarian cancer; euxanthone
Affiliations: Qingdao Hiser Hospital of Qingdao University  Qingdao Shandong China

Abstract:  Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers. Euxanthone, an active ingredient of the medicinal plant Polygala caudata, exhibits a selective cytotoxic effect in tumour cells. The present study was aimed to determine whether euxanthone could suppress ovarian tumour growth, and to study the relevant mechanism. Two EOC cell lines, SKOV3 and A2780, were used as the in vitro model and treated with euxanthone. Cell viability and apoptosis were assayed using Cell Counting Kit-8 (CCK-8) and Annexin-V FITC/PI staining, respectively. Commercially available kits were used to measure the glucose consumption, lactate production, and intracellular ATP levels. Western blots assay was conducted to examine the level of apoptotic markers. To examine the roles of HK2 and STAT3 in the anti-tumour effect of euxanthone, cells were transfected with vectors overexpressing HK2 or STAT3, and assayed as above. Finally, SKOV3 cells were injected to mice models to appreciate the anti-neoplastic effect of euxanthone in vivo. We found that euxanthone impaired the cell viability and induced apoptosis via the intrinsic pathway in a concentration-dependent fashion in both SKOV3 and A2780 cells. Euxanthone also caused inhibition of glycolysis. Apoptosis and glycolysis inhibition was mediated by the downregulation of HK2, which in turn was a result of STAT3 inactivation. In vivo experiments also supported that euxanthone could exert anti-cancer activities without general toxicity. In conclusion, euxanthone triggered mitochondrial apoptosis and inhibited glycolysis in EOC cells. Significance of the study: Euxanthone triggered mitochondrial apoptosis and inhibited glycolysis in EOC cells. Our findings provide preliminary experimental data that support further studies on the potential therapeutic role of euxanthone in ovarian cancer. 

Retracted: Yes

PubPeer comments:
 Fig 1E: ![] Xylocampa Areola previously spotted the same unexpectedly-similar FACSimiles in [Yang et al (2019)] and in [Liu et al (2018)] . ![] , 
 Fig 1E again: ![file] ...and FIg 3E,  Flow cytometric analysis showed that overexpression of HK2 decreased the proportion of apoptotic [SKOV3 and A2780] cells . ![file] Fig 5D is more of the same, and I am not inclined to give it any more attention than it received from the Editor and reviewers. ![file] , 
 Here are galleries of histology slices from four papers, with four non-overlapping teams of nominal authors, sharing surprisingly many slices in common. Identication of each slice in terms of treatment and immunohistochemistry stain is arbitrary. There are more duplicates but I lost interest when I ran out of colors. Upper left: Fig 6D from [Wang et al (2018)] . Physcion 8-O-u03b2-glucopyranoside and clear-cell renal cell carcinoma. Middle left: 8D from [Dou et al (2019)] . Physcion 8-O-u03b2-Glucopyranoside and Testicular Germ Cell Tumors. Upper right: 7E from [Niu et al (2019)] . Physcion 8-O-u03b2-glucopyranoside and gastric cancer. Lower: 6C from [Zou et al (2018)] . Euxanthone and epithelial ovarian cancer. ![] , 
 Fig 6c *[bottom]*. One tissue slice also appears in 4G from [Shen et al (2019)] *[at top]*, **and** in 8D from [Dou et al (2019)] *[middle]*. Differently identified. No authors in common. ![file] , 
 Fig 6C *[bottom]*. Tissue samples also appear in 8C from [Liu et al (2018)] [left] **AND** in 7E from [Niu et al (2019)] *[right]*. Differently identified. No authors in common. ![] , 
 Here are galleries of histology slices from **six** papers, with **six** non-overlapping teams of nominal authors, sharing surprisingly many slices in common. Identication of each slice in terms of treatment and immunohistochemistry stain is arbitrary. Focussing on connections to the uppermost image, due to lack of colors to show other inter-relationships. Clockwise from top: Fig 7F from [Pan et al (2018)] . Physcion and hepatoceullar carcinoma. 7E from [Niu et al (2019)] . Physcion 8-O-u03b2-glucopyranoside and gastric cancer. Fig 6D from [Wang et al (2018)] . Physcion 8-O-u03b2-glucopyranoside and clear-cell renal cell carcinoma. 6C from [Zou et al (2018)] . Euxanthone and epithelial ovarian cancer. 8C from [Liu et al (2018)] . Hispidulin and colorectal cancer. 8D from [Dou et al (2019)] . Physcion 8-O-u03b2-Glucopyranoside and Testicular Germ Cell Tumors. ![] , 
 *[Below]* Fig 6C. *[At upper left]* Fig 8 E:  Soy B treatment elevated the expression of cleaved caspase-3 and Bax while repressed the expression of Bax and SphK1 . From [Wang et al (2018)] . *[Upper right]* Fig 3 E [Amentoflavone]  . increased levels cleaved caspase-3 and decreased the ratio of Bcl-2 Bax (200u00d7) . From [Liu Yu (2018)] . ![file] Surprisingly many tissue slices in common. Identication of each slice in terms of treatment and immunohistochemistry stain is arbitrary. Other slices are shared with other papers from the same oeuvre. , 
 Retracted [18 January 2021] . ------------------------------------- The above article, published online on July 8, 2018 in Wiley Online Library , has been retracted by agreement between the journalu2019s Editor in Chief, Prof. Dr. Martin Hewinson, and John Wiley Sons Ltd. The retraction has been agreed following an investigation based on allegations raised by a third party, concerning similarities to images published elsewhere. Raw data could not be provided and thus the validity of the overall results could not be confirmed. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction. , 
 Haici Medical Group announced the results of an investigation on [14 October 2021](http: www.qdhaici.cn news_detail newsId=3381.html). Thanks to Google Translate for the translation. ---------------------- 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. The paper  Euxanthone Inhibits Glycolysis and Triggers Mitochondria-Mediated Apoptosis by Targeting Hexokinase 2 in Epithelial Ovarian Cancer published by Wang Haijing as the corresponding author and Zou Jun as the first author . After investigation, there are data tampering, fabrication of research processes, and improper signatures. Academic misconduct. The relevant responsible personnel shall be dealt with as follows: - 1. To the first author Zou Jun: talk about scientific research integrity and admonishment; publicly report criticism in the hospital; immediately contact the magazine to withdraw the paper involved; withdraw the scientific research award; cancel the five-year application or application for science and technology plan projects, science and technology awards, and science and technology talent titles Cancel the five-year professional and technical promotion qualification; cancel the deputy senior title obtained thereby. - 2. To the corresponding author Wang Haijing: talk about scientific research integrity; publicly report criticism in the hospital; immediately contact the magazine to withdraw the paper involved; cancel the five-year application or application for science and technology plan projects, science and technology awards, and science and technology talent titles; cancel the five-year professional skills Qualifications for promotion. - 3. To Wang Yamei (second author), Zheng Wenjian (fifth author), Gao Qian (sixth author): talks on scientific research integrity and admonitions; public notification and criticism in the hospital; cancellation of one-year applications or applications for science and technology plan projects, science and technology awards, and science and technology talents Title qualification; cancellation of professional and technical post promotion qualifications for one year. - 4. To the third author Liu Mingdi: talks on scientific research integrity and admonition; public notification and criticism in the hospital; cancellation of one-year application or application for science and technology plan projects, science and technology awards, science and technology talent title qualifications; cancellation of professional and technical post promotion qualifications for one year; cancellation of the obtained qualifications Intermediate title. ,