Effect of Rapamycin on the Cell Cycle Arrest of T Lymphocytes.
- Author:
Jeong Sam LEE
1
;
Chul HAN
;
Soo Jin Na CHO
;
Sang Young CHUNG
Author Information
1. Department of Surgery, Chonnam National University Medical School, Gwangju, Korea. sycpvts@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
Rapamycin;
Apoptosis;
Molt-4 T cell;
Cytotoxicity
- MeSH:
Apoptosis;
bcl-2 Homologous Antagonist-Killer Protein;
Cell Cycle Checkpoints*;
Cell Cycle*;
Cell Survival;
Fibroblasts;
Flow Cytometry;
Hepatocytes;
Humans;
Reactive Oxygen Species;
S Phase;
Signal Transduction;
Sirolimus*;
T-Lymphocytes*
- From:Journal of the Korean Surgical Society
2007;73(1):13-20
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Rapamycin (RPM) and its analogues are known for their potent immunosuppressant and anti-proliferative properties, which stem from their ability to modulate the signal transduction pathways involved in cell cycle progression from the G1 to S phase. Thus, RPM has been shown to inhibit the proliferation of a number of non-immune cell types, including hepatocytes, vascular smooth cells and fibroblasts. In addition to its effects on proliferation, RPM may also play a role in the regulation of apoptosis under certain circumstances. METHODS: The effects of RPM on the activation, proliferation and expression of cytotoxic effector molecules were examined on Molt-4 human T-lymphocyte by determining its effects on apoptosis, cell viability, reactive oxygen species (ROS) production and mitochondrial dysfunction. Cells were cultured in the presence or absence of RPM, and then analyzed by Flow cytometry after staining with PI (propidium iodide). RESULTS: The viability of Molt-4 T cells dose- and time-dependently decreased on the addition of RPM. CONCLUSION: RPM induced cytotoxicity was characterized by G2/M phase cell cycle arrest. In addition, a pharmacological scavenging study of ROS, including H2O2, revealed the cytotoxicity was mainly induced by the generation of ROS, which might modulate the expression of Bak protein and mitochondrial dysfunction.
