Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway
Authors: Hongwei Yu
Manman Xu
Tongchong Zhou
Wenjin Huang
Xingyuan Shi
Kai Luo
Journal: Experimental and Therapeutic Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; bergenin; cell cycle; cell migration; cervical cancer.
Affiliations: Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China, The Research Institute, Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China

Abstract:  Bergenin is a secondary metabolite that may be primarily isolated from Bergenia species. Although it has been found to exhibit significant biological activities, the anticancer activity of bergenin against cervical cancer cells has not been explored. The present study was designed to evaluate the anticancer effects of bergenin on HeLa cervical cancer cells. The results showed that bergenin reduced the cell viability of the HeLa cervical cancer cells in a dose-dependent pattern. However, the anticancer effects of bergenin were found to be comparatively lower on the normal cervical cells. Furthermore, the anticancer effects of bergenin were primarily found to be due to induction of apoptosis in the HeLa cervical cancer cells. Notably, bergenin also enhanced the expression of Bax and decreased the expression of Bcl-2. WThe effect of bergenin on cell cycle phase distribution of HeLa cells was also investigated and it was found that bergenin could induce G0/G1 cell cycle arrest. Furthermore, bergenin could also inhibit the migration of HeLa cancer cells as well as the phosphorylation of STAT3. Taken together, bergenin may be a promising candidate for the management of cervical cancer. 

Retracted: Yes

PubPeer comments:
 Figure 6.  Bergenin triggers G0 G1 cell cycle arrest in HeLa cervical cancer cells at indicated concentrations. ![file] Panels for 7.5, 15 and 30 microM are the same. , 
 *[right]* Figure 3 from [Shi et al (2019)] .  Bergenin induces apoptosis in HeLa cervical cancer cells at indicated concentrations. *[left]* Fig. 2 from [Zeng et al (2019)] .  DAPI staining showing the induction of apoptosis in the CH157-MN cells at indicated concentrations of chrysophanol. ![file] Fig 2 from Zeng et al also overlaps with Figure 3 from[ Zhang et al (2020)] , here at right. Again, the panels are details from the present Fig 2. ![] , 
 *[right]* Figure 4.  Estimation of apoptotic HeLa cell populations by Annexin V PI staining at indicated concentrations of bergenin. Received December 13, 2017; Accepted June 26, 2018 *[left]* Figure 3 from [Zhang et al (2018)] .  Estimation of apoptotic of Saos-2 osteosarcoma cell populations at indicated concentrations of ludartin. Annexin-V propidium iodide (PI) staining. Received 2018.01.26; Published: 2018.07.16 ![file] , 
 Retracted [19 April 2021] .  Following the publication of the above paper, a concerned reader drew to the Editoru2019s attention that, in Fig. 6, the data panels shown for the experiments performed with 7.5, 15 and 30 u03bcM bergenin were strikingly similar in terms of their overall appearance. Furthermore, several figures contained data that bore striking similarities to data published in other papers; notably, the cellular data shown in Fig. 3 appeared to have been presented with a different field of view in Fig. 2 of another paper written by different authors and based at a different research institution [Zeng C, Guo B, Chen J and He W: Antitumor effects of chrysophanol in malignant optic nerve meningioma cell lines are mediated via caspase activation, induction of mitochondrial mediated apoptosis, mitochondrial membrane depolarization and targeting the mitogen-activated protein kinase signaling pathway. *Pharmacology* 104: 28-35, 2019].  After having conducted an independent investigation in the Editorial Office, the Editor of *Experimental and Therapeutic Medicine* has determined that this article should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. ,