Open AccessAntiproliferative effect of rapamycin on human T‐cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition 1
Author(s) -
ZHAO Yanmin,
ZHOU Qian,
XU Yun,
LAI Xiaoyu,
HUANG He
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00767.x
Subject(s) - jurkat cells , telomerase , cell cycle , telomerase reverse transcriptase , cell growth , biology , cell culture , cell cycle checkpoint , g1 phase , apoptosis , microbiology and biotechnology , pi3k/akt/mtor pathway , flow cytometry , protein kinase b , cancer research , signal transduction , t cell , immunology , biochemistry , genetics , immune system , gene
Aim: To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T‐cell leukemia cell line Jurkat. Methods : Cell proliferation was assessed after exposure to rapamycin by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progression and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi‐quantitative RT‐PCR. Results : Rapamycin inhibited the proliferation of Jurkat, induced G 1 phase arrest, unregulated the protein level of p21 as well as p27, and downregulated cyclinD3, phospho‐p70s6k, and phospho‐s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. Conclusion : Rapamycin displayed a potent antileukemic effect in the human T‐cell leukemia cell line by inhibition of cell proliferation through G 1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.