Girinimbine Inhibits the Proliferation of Human Ovarian Cancer Cells In Vitro via the Phosphatidylinositol-3-Kinase (PI3K)/Akt and the Mammalian Target of Rapamycin (mTOR) and Wnt/β-Catenin Signaling Pathways
Authors: An Muer
Qiu Xin
Journal: Medical Science Monitor (2018)
Discipline: CLINICAL MEDICINE
Keywords: ovarian cancer; girinimbine; cell proliferation; cell migration; apoptosis
Affiliations: Department of Obstetrics and Gynecology, Huashan Hospital North, Fudan University, Shanghai, China (mainland)., Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

Abstract:  BACKGROUND Worldwide, ovarian cancer is increasing in prevalence and has a high mortality rate. Girinimbine is a carbazole alkaloid isolated from Murraya koenigii (the curry tree) and is used in Chinese herbal medicine. The aim of this study was to evaluate the effects of girinimbine on cell proliferation, cell migration, and apoptosis in human ovarian cancer cells in vitro. MATERIAL AND METHODS A human ovarian cancer cell line panel, which included SKOV3 cells and the SV40 immortalized normal human ovarian cell line, were treated with increasing doses of girinimbine. Cell proliferation was evaluated using the MTT assay. Confocal immunofluorescence using 4',6-diamidino-2-phenylindole (DAPI), Annexin-V, and propidium iodide (PI) were used to measure cell apoptosis. Cell migration and invasion were determined by transwell assays. Protein expression was determined by Western blot. RESULTS Girinimbine inhibited SKOV3 ovarian cancer cell proliferation in a dose-dependent manner. The half maximal inhibitory concentration (IC50) of grinimbine was 15 µM for the SKOV3 cells, and 120 µM for the SV40 cells. Grinimbine treatment resulted in apoptosis of SKOV3 cells, from 2.2% in untreated cells to 58.8% at a dose of 30 µM, which was associated with an increase in the Bax/Bcl-2 ratio. Girinimbine inhibited cell migration and invasion of the SKOV3 cancer cells in vitro and inhibited the PI3K/AKT/mTOR and Wnt/β-catenin signaling pathways. CONCLUSIONS Girinimbine, a carbazole alkaloid used in Chinese herbal medicine, inhibited the proliferation and cell migration of human ovarian cancer cells in vitro, in a dose-dependent manner, via the PI3K/Akt/mTOR and Wnt/β-catenin signaling pathways. 

Retracted: Yes

PubPeer comments:
 *[above[* Fig 1D from [Yin et al (2019)] .  Colony formation of the NC and Si-PPMD1 transfected HT-29 cells . *[below]* Fig 4C from [Si et al (2019)] .  Colony formation of NC and pcDNA-CUL5 transfected SK-OV3 and OVACAR-3 cells . ![file] Different cell-lines, conditions and authors. Same image. , 
 #1 [above[ Fig 1D from [Yin et al (2019)] .  Colony formation of the NC and Si-PPMD1 transfected HT-29 cells . [below] Fig 4C from [Si et al (2019)] .  Colony formation of NC and pcDNA-CUL5 transfected SK-OV3 and OVACAR-3 cells . ![file] For comparison with *[left]* Figure 2 from [Zhou et al (2020)] .  Colony formation assay showing inhibition of colony formation of MML-1 melanoma cells at indicated concentrations of Heptazoline . ![file] , 
 There appear to be two versions of this paper in circulation. The version [currently provided by the journal website] has a different Fig 1D from one [archived at ResearchGate] . ![file] According to PDF metadata, the current version was modified on 30 December 2020 (02:24:02 AM). Perhaps the paper was revised or amended subsequent to my comments above. The ResearchGate version was modified on 8 August 2019 (02:51:38 PM). ,