PMID- 30084434
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20240329
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 24
DP  - 2018 Aug 7
TI  - 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/beta-Catenin Signaling Pathways.
PG  - 5480-5487
LID - 10.12659/MSM.910137 [doi]
AB  - 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 microM for the SKOV3 cells, and 120 microM 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 microM, 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/beta-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/beta-catenin signaling pathways.
FAU - Xin, Qiu
AU  - Xin Q
AD  - Department of Obstetrics and Gynecology, Huashan Hospital North, Fudan 
      University, Shanghai, China (mainland).
FAU - Muer, An
AU  - Muer A
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin 
      Medical University, Harbin, Heilongjiang, China (mainland).
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20180807
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Alkaloids)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (beta Catenin)
RN  - 23095-44-5 (girinimbine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
RIN - Med Sci Monit. 2021 Mar 11;27:e931225. PMID: 33704262
MH  - Alkaloids/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/*drug therapy/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Wnt Signaling Pathway/*drug effects
MH  - beta Catenin/metabolism
PMC - PMC6094984
EDAT- 2018/08/08 06:00
MHDA- 2018/12/12 06:00
PMCR- 2018/08/07
CRDT- 2018/08/08 06:00
PHST- 2018/08/08 06:00 [entrez]
PHST- 2018/08/08 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/08/07 00:00 [pmc-release]
AID - 910137 [pii]
AID - 10.12659/MSM.910137 [doi]
PST - epublish
SO  - Med Sci Monit. 2018 Aug 7;24:5480-5487. doi: 10.12659/MSM.910137.