RETRACTED: Lupeol Induces Apoptosis and Cell Cycle Arrest of Human Osteosarcoma Cells Through PI3K/AKT/mTOR Pathway
Authors: Yan Liu
Wei Dai
Liqiang Qian
Gang Wang
Tingting Bi
Genhai Shen
Quangen Gao
Journal: Technology in Cancer Research & Treatment (2016)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/AKT/mTOR; apoptosis; cell cycle; lupeol; osteosarcoma.
Affiliations: Department of General Surgery, Wujiang No.1 People's Hospital, Suzhou, China., Department of Geriatric Ward, Wujiang No.1 People's Hospital, Suzhou, China., Department of General Surgery, Wujiang No.1 People's Hospital, Suzhou, China  .

Abstract:  Lupeol, a dietary triterpene present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including anticancer effect in vitro and in vivo However, the activity of lupeol against osteosarcoma remains unclear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of lupeol on human osteosarcoma cells (MNNG/HOS and MG-63) in vitro and in vivo MNNG/HOS and MG-63 cells were treated by lupeol and subjected to methyl thiazolyl tetrazolium analysis, Hoechst staining, annexin V/propidium iodide double staining, cell cycle analysis, and Western blot analysis. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and lupeol was intravenously administered to evaluate the anticancer capacity in vivo Our results showed that lupeol induced apoptosis as well as cell cycle arrest in G0/G1 phase of MNNG/HOS and MG-63 cells in a dose-dependent manner in vitro Furthermore, the protein expression levels of phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT), p-p70S6K, and cyclin D1 were significantly downregulated, whereas the expression levels of p21 and p27 were upregulated. These protein interactions may play a pivotal role in the regulation of apoptosis and cell cycle arrest. More importantly, our in vivo studies showed that administration of lupeol decreased tumor growth in a dose-dependent manner and has no significant effect on the function of liver and kidney. Taken together, our findings indicated that lupeol can induce apoptosis as well as cell cycle arrest of human osteosarcoma cells through phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway and might offer a promising new approach in the effective treatment of osteosarcoma. 

Retracted: Yes

PubPeer comments:
 Retracted [6 October (2015)] . Suggested by a colleague. ------------------------------------------------------- The following article has been retracted as a result of our determining the likelihood of manipulation of the peer-review process: u201cLupeol Induces Apoptosis and Cell Cycle Arrest of Human Osteosarcoma Cells Through PI3K AKT mTOR Pathway,u201d by Yan Liu, MD, Tingting Bi, MD, Wei Dai, PhD, Gang Wang, PhD, Liqiang Qian, MD, Genhai Shen, MD, and Quangen Gao, MD, Technology in Cancer Research Treatment, DOI: 10.1177 1533034615609014 After investigating the peer-review process for the article, SAGE determined that the peer-review process was likely compromised. Our review identified an unusual verbatim repetition of review comments provided from different peer-reviewer accounts provided by submitting author, Quangen Gao, MD, as recommended reviewers. SAGE apologizes to readers and regrets that the academic record has been compromised as a result of this manipulation of the peer-review process. , 
 *[left]* Fig 5.  Lupeol treatment altered the expression of related molecules in human osteosarcoma cells. A and D, Expression of PI3K, p-PI3K, AKT, p-AKT, mTOR, p-mTOR, p70S6K, p-p70S6K, cyclin D1, p21, and p27 was analyzed by Western blot assay. Glyceraldehydes 3- phosphate dehydrogenase (GAPDH) was used as the sample loading control. *[right]* Figure 4 from [Liu et al (2016)] .  Oxymatrine treatment altered the expression of apoptosis-related molecules in human hepatoma cells. A, Expression of Bax, Bcl-2, and caspase 3 was analyzed by Western blot assay. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the sample loading control. Unexpected similarity of the control bands. ![file] , 
 Thank you very much for reminding us of the repetition. Indeed, we made a mistake during the figure 4 preparation. We may have used Fig5 as a template for Fig 4 and forget replacing the control bands. We will further verify and correct any errors in time. Surely, I will ask the journal for the correction soon. Thank you for your review, and we appreciate it. ,