Bergamottin isolated from Citrus bergamia exerts in vitro and in vivo antitumor activity in lung adenocarcinoma through the induction of apoptosis, cell cycle arrest, mitochondrial membrane potential loss and inhibition of cell migration and invasion
Authors: Hong-Zhi Zou
Hui-Juan Wu
Yan-Qiu Zhao
Hong-Bo Wu
Li-Juan Chen
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: bergamottin; anticancer properties; non-small cell lung carcinoma; A549 cells; cell proliferation
Affiliations: Department of Internal Medicine, The Affiliated Tumor Hospital of Zhengzhou University/Tumor Hospital of Henan Province, Zhengzhou, Henan 450008, P.R. China.

Abstract:  The objective of the present study was to investigate the in vitro and in vivo anticancer properties of bergamottin, a natural furanocoumarin, against human non-small cell lung carcinoma (NSCLC) A549 cells. We also studied its effect on cell proliferation, cell cycle arrest, cell invasion, cell migration as well as cell apoptosis. Antiproliferative activity of bergamottin was estimated by the MTT assay. Phase contrast and fluorescence microscopy as well as flow cytometry using Annexin V-FITC assay were used to study induction of apoptosis by bergamottin in these cells. The effects of bergamottin on cell cycle phase distribution as well as on mitochondrial membrane potential were also demonstrated using flow cytometry. In vitro wound healing assay was used to study the effect of bergamottin on cell migration. The effects of bergamottin on tumor progression were also observed using a nude mouse model. The mice were divided into 4 groups and treated with bergamottin injected intraperitoneally. Bergamottin induced dose-dependent as well as time-dependent cytotoxic effects as well as inhibition of colony formation in the A549 cancer cells. Bergamottin also suppressed cancer cell invasion as well as cancer cell migration. Phase contrast microscopy and fluorescence microscopy revealed that bergamottin induced cell shrinkage, chromatin condensation and the cells became rounded and detached from each other. Bergamottin also induced a potent cell cycle arrest at the G2/M phase of the cell cycle. Experiments in mice showed that 25, 50 and 100 mg/kg bergamottin injection reduced the tumor weight from 1.61 g in the phosphate-buffered saline (PBS)-treated group (control) to 1.21, 0.42 and 0.15 g in the bergamottin-treated groups, respectively. The results of the present study revealed that bergamottin was able to inhibit lung cancer cell growth both in a cell model and a xenograft mouse model by inducing apoptosis, mitochondrial membrane potential loss, G2/M cell cycle arrest as well as inhibiting cell migration and invasion. 

Retracted: Yes

PubPeer comments:
 This paper is a total falsification, seen by the fabricated  micrographs in Figure 6, 8 and 9, where areas are cloned. I have marked a few examples. There are apparently no peer reviewing for Oncology Reports. ![file] , 
 #1 It doesn t seem that Fig 12 was designed to be looked at closely. ![file] , 
 Fig 10. ![file] , 
 Retracted [19 April 2021] .  Following the publication of the above paper, a concerned reader drew to the Editor s attention that a number of figures (specifically, Figs. 6, 8, 9, 10 and 12) contained apparent anomalies, including repeated patternings of data within the same figure panels.  After having conducted an independent investigation in the Editorial Office, the Editor of Oncology Reports has determined that this paper 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. ,