Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

Wallax A S Ferreira1, Rommel R Burbano2,3,4, Claudia do Ó Pessoa5

  • 1Laboratorio de Cultura de Tecidos e Citogenetica, SAMAM, Instituto Evandro Chagas, Ananindeua, Para, Brazil.

Abstract

Insights

Pisosterol effectively halts glioma cell growth and induces apoptosis by regulating key cell cycle genes. This natural compound shows promise as an anticancer agent, primarily through the ATM/ATR signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Pisosterol, a triterpene from Pisolithus tinctorius, shows potential anticancer activity.
  • The specific molecular mechanisms of pisosterol's effects on glioma cells are not well understood.

Purpose of the Study:

  • To investigate the antitumoral effects of pisosterol on glioma cell lines.
  • To elucidate the molecular mechanisms underlying pisosterol's action on glioma cells.

Main Methods:

  • Cell viability and proliferation assessed using MTT and trypan blue assays.
  • Cell cycle distribution analyzed via flow cytometry.
  • Gene and protein expression, along with promoter methylation, analyzed using RT-qPCR, western blotting, and BSP-PCR for key cancer-related genes.

Main Results:

  • Pisosterol dose-dependently reduced glioma cell viability and proliferation.
  • Induced G2/M cell cycle arrest and apoptosis.
  • Modulated expression of genes including ATM, CASP3, MYC, and TP53, activating caspase-dependent and -independent apoptotic pathways.

Conclusions:

  • Pisosterol induces G2/M arrest and apoptosis in glioma cells.
  • The ATM/ATR signaling pathway is crucial for pisosterol-mediated cell cycle arrest.
  • Pisosterol is a potential anticancer candidate for further glioma research.

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