Tubeimoside‑1 induces apoptosis in human glioma U251 cells by suppressing PI3K/Akt‑mediated signaling pathways

Mol Med Rep. 2020 Aug;22(2):1527-1535. doi: 10.3892/mmr.2020.11224. Epub 2020 Jun 11.

Abstract

Tubeimoside-1 (TBMS1), a traditional Chinese herb extracted from Bolbostemma paniculatum (Maxim.), induces apoptosis in a number of human cancer cell lines. TBMS1 has been reported to induce apoptosis in human glioma cells, however the mechanism remains to be elucidated. The present study explored TBMS1‑induced PI3K/Akt‑related pathways in human glioma cells. The human glioma U251 and the human astrocyte (HA) cell lines were treated with various concentrations of TBMS1. MTT assays were conducted to analyze cell viability. Cell cycle distribution and the rate of apoptosis were assessed using flow cytometry. BrdU incorporation and Hoechst 33342 staining were performed to analyze the cell cycle and apoptosis, respectively. Western blotting was performed to investigate protein expression levels. The results demonstrated that TBMS1 reduced cell viability in human glioma cells U251 by suppressing Akt phosphorylation. Subsequently, TBMS1 inhibited DNA synthesis and induced G2/M phase arrest by targeting the PI3K/Akt/p21 and the cyclin‑dependent kinase 1/cyclin B1 signaling cascades. In addition, TBMS1 triggered apoptosis via the PI3K/Akt‑mediated Bcl‑2 signaling pathway. These results demonstrated that TBMS1 prevented the progression of gliomas via the PI3K/Akt‑dependent pathway, which provided a theoretical basis for in vivo studies to use TBMS1 as potential therapy for the prevention of cancer.

Keywords: apoptosis; cell cycle; glioma; tubeimoside-1; Pi3K/akt.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Astrocytes
  • CDC2 Protein Kinase / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin B1 / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Glioma / drug therapy
  • Glioma / pathology*
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • BCL2 protein, human
  • CCNB1 protein, human
  • Cyclin B1
  • Proto-Oncogene Proteins c-bcl-2
  • Saponins
  • Triterpenes
  • tubeimoside I
  • Proto-Oncogene Proteins c-akt
  • CDC2 Protein Kinase
  • CDK1 protein, human