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Updated: Jun 28, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Rapamycin-induced cytotoxic signal transduction pathway

S J N Choi1, H S You, S Y Chung

  • 1Division of Transplantation Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea. choisjn@chonnam.ac.kr

Transplantation Proceedings
|October 22, 2008
PubMed

Insights

Rapamycin decreases Molt-4 T lymphocyte viability by inducing reactive oxygen species (ROS) and G2/M cell cycle arrest. This cytotoxicity involves mitochondrial dysfunction and altered Bak protein expression, not caspase activation.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Rapamycin is an immunosuppressant drug with known effects on cell signaling.
  • Understanding rapamycin's impact on T lymphocyte function is crucial for its therapeutic applications.
  • Molt-4 cells are a human T lymphocyte cell line commonly used in immunological studies.

Purpose of the Study:

  • To investigate the effects of rapamycin on Molt-4 human T lymphocyte activation, proliferation, and cytotoxic molecule expression.
  • To determine rapamycin's impact on cell viability, cell cycle progression, and apoptosis-related pathways.

Main Methods:

  • Molt-4 cells were treated with varying concentrations and durations of rapamycin.
  • Cell viability was assessed using propidium iodide staining and flow cytometry.
  • Western blotting was employed to analyze protein expression (Bcl-2, Bak, p53, p21, p27, Rb, CDK2, cyclin B1), alongside measurements of reactive oxygen species (ROS) and mitochondrial membrane potential.

Main Results:

  • Rapamycin reduced Molt-4 cell viability in a dose- and time-dependent manner.
  • Increased reactive oxygen species (ROS) generation and mitochondrial membrane potential changes were observed.
  • G2/M phase cell cycle arrest occurred, characterized by decreased CDK2 and cyclin B1 expression, with no significant changes in caspase activity or expression of Bcl-2, p53, p21, p27, or Rb proteins.

Conclusions:

  • Rapamycin induces cytotoxicity in Molt-4 T lymphocytes via ROS generation, leading to mitochondrial dysfunction.
  • The observed G2/M cell cycle arrest is associated with reduced CDK2 and cyclin B1 levels.
  • These findings highlight a distinct mechanism of rapamycin-induced T cell death independent of classical apoptosis pathways.

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