Anticancer Effects of Gingerol in Retinoblastoma Cancer Cells (RB355 Cell Line) Are Mediated via Apoptosis Induction, Cell Cycle Arrest and Upregulation of PI3K/Akt Signaling Pathway
Authors: Hongyi Ii
Bo Meng
Wei Qu
Huiping Yuan
Journal: Medical Science Monitor (2018)
Discipline: CLINICAL MEDICINE
Keywords: gingerol; antiproliferative activity; RB355; retinoblastoma; cancer cells
Affiliations: Department of Ophthalmology, The 2nd Affiliated University Hospital, Harbin, Heilongjiang, China (mainland)., Health Center of Heilongjiang University, Harbin, Heilongjiang, China (mainland).

Abstract:  BACKGROUND The main aim of the current investigation was to study the antiproliferative activity of gingerol in RB355 human retinoblastoma cancer cells. The effects of gingerol on apoptosis induction, cell cycle arrest, and PI3K/Akt signaling pathway were also evaluated. MATERIAL AND METHODS MTT cell viability assay was used to assess the cytotoxic effects of gingerol in these cells while. To study apoptotic effects in these cells, we used inverted microscopy along with fluorescence microscopy using acridine orange/propidium iodide and Hoechst 33258 as staining dyes. Flow cytometry was used to study cell cycle phase distribution and Western blot assay indicated effects on PI3K/Akt protein expression levels. RESULTS Results showed that gingerol exerted dose-dependent and time-dependent growth inhibitory effects in these retinoblastoma cells. However, the growth inhibitory effects of gingerol were less pronounced against normal fr2 cells. As compared to the untreated control cells, gingerol-treated cells at concentrations of 25, 75, and 150 μM had drastic changes in cell morphology, including rounding and withering of cells, with disorganized cell layers. Gingerol-treated cells exhibited bright fluorescence, indicating rupture of the cell membrane. These results were further confirmed by acridine orange/propidium iodide staining, in which untreated cells showed normal green fluorescence and gingerol-treated cells showed yellow/red fluorescence. Gingerol also led to dose-dependent G2/M phase cell cycle arrest in RB355 retinoblastoma cells, as well as concentration-dependent activation of PI3K-related protein expressions. CONCLUSIONS Gingerol exhibits potent anticancer effects in RB355 human retinoblastoma cancer cells and these effects were mediated via apoptosis induction, cell cycle arrest, and modulation of the PI3K/Akt signaling pathway. 

Retracted: Yes

PubPeer comments:
 Retracted 29 December 2018. https: www.ncbi.nlm.nih.gov pmc articles PMC6324863  The article is withdrawn by the authors request. Cited 9 times, all in 2019 or 2020, subsequent to retraction. Figure 4.  Gingerol induced apoptosis in RB355 human retinoblastoma cells after the cells were treated with 0 (A), 25 (B), 75 (C), and 150 u03bcM (D) dose of gingerol for 48 h. The cells were then stained with Hoechst 33258 and finally analyzed by fluorescence microscopy at u00d7200 magnification. Orange arrows indicate cells undergoing apoptotic morphological changes, including chromatin condensation, cell shrinkage, and membrane blebbing. Panel B is basically a copy of A, after a 180-deg flip. All panels are clearly copy-paste composites. How was this ever published? ![file] , 
 Fig 5.  Gingerol induced apoptosis in RB355 human retinoblastoma cells after the cells were treated with 0 (A), 25 (B), 75 (C), and 150 u03bcM (D) dose of gingerol for 48 h. The cells were then stained with AO PI double-staining dye and finally analyzed by fluorescence microscopy at u00d7200 magnification. Yellow arrows indicate cells undergoing apoptosis, viable cells emit green fluorescence, and apoptotic cells emit yellow or red fluorescence. ![file] (D) is clearly based on (C) (or vice versa) after a 180-deg flip and various alterations. (A) and (B) are copy-paste composites. ,