Lupeol inhibits growth and migration in two human colorectal cancer cell lines by suppression of Wnt-β-catenin pathway
Authors: Longjin Jin
Dan Hong
Yuqin Qian
Xinlong Kong
Xianhong Yang
Sijia Shao
Yihao Wang
Keke Wang
Zhefeng Lou
Xuezi Tu
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: Wnt; apoptosis; colorectal cancer; lupeol; migration
Affiliations: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Zhejiang, People's Republic of China, ; ., School of Ophthalmology and Optometry, Wenzhou Medical University, Zhejiang, People's Republic of China., School of the first Clinical Medical Sciences, Wenzhou Medical University, Zhejiang, People's Republic of China.

Abstract:  Background: Lupeol, a triterpene isolated from various herbal plants, possesses an anti-inflammatory function and has been proposed as a candidate for anticancer agents. The purpose of this research was to investigate the effect of lupeol on the viability, apoptosis, cell-cycle distribution, and migration of colorectal cancer cell lines and its molecular mechanism. Methods: Lupeol was assessed for its anticancer effect using two human colorectal cancer cell lines: SW480 and HCT116. These cells were treated with lupeol, and their viability, apoptosis, migration, and cycle distribution were detected by CCK8, flow cytometry, and the transwell method. Quantitative PCR, Western blot, and immunofluorescence were applied to detect the expressions of CTNNB1, TCF4, cMYC, CCND1, CLDN1, and CCNA2. Results: Lupeol suppressed cell viability and migration and induced cellular apoptosis of both cell lines, with increased p53 and decreased Bcl2 protein levels (P&lt;0.05). Cell cycles of both lupeol-treated cell lines were arrested in the S phase (P&lt;0.05). Quantitative PCR and Western blot analyses showed significantly reduced expressions of CTNNB1, TCF4, and downstream genes of the Wnt-β-catenin pathway, including the cell-cycle-regulated genes of cMYC and CCND1 of both cell lines upon lupeol treatment (P&lt;0.05). mRNA and protein levels of CLDN1 decreased in HCT116 cells, plus the expression of CCNA2 mRNA and protein decreased in SW480 cells (P&lt;0.05). Immunofluorescence analysis confirmed decreased expression of Wnt-β-catenin signaling. Conclusion: Our findings indicate that lupeol effectively inhibits proliferation and migration and induces apoptosis and cell-cycle arrest of two colorectal cell lines by inactivation of the Wnt-β-catenin signaling pathway and downregulation of cMYC, CCND1, CCNA2, and CLDN1, thereby making it a promising anticancer candidate. 

Retracted: Yes

PubPeer comments:
 There seems to be a duplicated Western blot in Figs 6 B and D: ![file] , 
 Hi, Dr. Areola Thanks for pointing the error! The errors due to editing the results are shown below. When we were preparing the results in the top strip of Figure 6D, we mistakenly copied the data of the SW480 group, and the data of the HCT116 group was omitted. And, the percentage in the HCT116 group was correct. We will communicate with the editor of OncoTargets and Therapy for correction, and the corrected data will be published soon. ![file] Yours sincerely, Yihao Wang , 
 2020 retraction. https: www.dovepress.com retraction-lupeol-inhibits-growth-and-migration-in-two-human-colorecta-peer-reviewed-article-OTT Wang YH, Hong D, Qian YQ, et al. Onco Targets Ther. 2018;11:7987u20147999. The Editor-in-Chief and Publisher of OncoTargets and Therapy wish to retract the published article. We were notified of the alleged duplication of western blot bands between Figure 6B Cyclin A2 and 6D Cyclin A2 in the published paper. The authors provided an explanation for the duplication but were unable to provide satisfactory raw data for the western blots shown in the article. The editor determined the findings of the study could no longer be supported and requested for the article to be retracted. The authors wish to apologise for this error. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,