The inhibitory effects of ginsenoside Rd on the human glioma U251 cells and its underlying mechanisms

J Cell Biochem. 2019 Mar;120(3):4444-4450. doi: 10.1002/jcb.27732. Epub 2018 Sep 27.

Abstract

Objective: The current study was designed to investigate the inhibitory effects of ginsenoside Rd (Gs-Rd) on human glioma U251 cells in vitro and its possible underlying mechanisms.

Methods: The groups included blank control group, low concentration Gs-Rd treatment group (20 μM), mid concentration Gs-Rd treatment group (40 μM), and high concentration Gs-Rd treatment group (80 μM). The proliferative activity of human glioma U251 cells was detected by the MTT assay. Flow cytometry was performed to measure cell apoptosis of human glioma U251 cells. In addition, the ELISA assay was used to measure the telomerase activities in different groups on 24 hours, 48 hours, and 72 hours. Furthermore, real-time quantitative polymerase chain reaction (RT-PCR) and Western blot analysis were performed to measure the expression of Bcl-2, human telomerase catalytic subunit (hTERT), and caspase-3 in different groups on 48 hours at both messenger RNA (mRNA) and protein levels.

Results: The proliferation of U251 cells was inhibited by Gs-Rd with different concentrations in the dose- and time-dependent manners. In addition, Gs-Rd promoted U251 cell apoptosis rate in a dose-dependent manner. Gs-Rd with different concentrations (20 μM, 40 μM, and 80 μM) significantly enhanced the expression of teleomerase on 24 hours and 48 hours. In addition, Gs-Rd with different concentrations significantly increased caspase-3 and decreased Bcl-2 and hTERT expressions at both mRNA and protein levels.

Conclusion: The Gs-Rd can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to inhibiting telomerase activity, downregulating expression of Bcl-2 and hTERT, and upregulating expression of caspase-3 of human glioma U251 cells.

Keywords: Bcl-2; U251; apoptosis; caspase-3; ginsenoside Rd; human telomerase catalytic subunit (hTERT); telomerase.

MeSH terms

  • Caspase 3 / biosynthesis*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Ginsenosides / pharmacology*
  • Glioma* / drug therapy
  • Glioma* / metabolism
  • Glioma* / pathology
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Telomerase / biosynthesis*

Substances

  • BCL2 protein, human
  • Ginsenosides
  • Proto-Oncogene Proteins c-bcl-2
  • TERT protein, human
  • Telomerase
  • CASP3 protein, human
  • Caspase 3
  • ginsenoside Rd