Akt Phosphorylation Orchestrates T11TS Mediated Cell Cycle Arrest in Glioma Cells

Cancer Invest. 2021 Nov;39(10):854-870. doi: 10.1080/07357907.2021.1986060. Epub 2021 Oct 11.

Abstract

The novel anti-neoplastic glycopeptide T11TS retards glioma both in in-vitro clinical samples and in-vivo models. This study investigates the correlation between altering the glioma microenvironment with glioma arrest and death. Flow cytometry, immunoblotting, ELISA, and co-immunoprecipitation were employed to investigate glioma cell arrest and death. Results include a decline in phosphorylation of Akt and attenuation of p21 phosphorylation (Thr145,Ser146) and disassociation of p-Akt-Mdm2 and p-Akt-BAD facilitating death by Akt>BAD. T11TS influence phosphorylation patterns in two focal axes Akt>p21 and Akt>Mdm2>p53. The current article provides crucial insight in deciphering the mechanism of T11TS induced glioma cell arrest and death.

Keywords: Akt; Glioma; T11TS; apoptosis; cell cycle arrest.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • CD58 Antigens / pharmacology*
  • CD58 Antigens / therapeutic use
  • Cell Cycle Checkpoints / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Male
  • PTEN Phosphohydrolase / analysis
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / analysis
  • Rats
  • Rats, Wistar
  • Tumor Microenvironment
  • Tumor Suppressor Protein p53 / analysis
  • bcl-Associated Death Protein / metabolism

Substances

  • CD58 Antigens
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • T11TS protein, sheep
  • Tumor Suppressor Protein p53
  • bcl-Associated Death Protein
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase