title: Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition.
abstract: OBJECTIVE
  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 G1 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.
  
  
  CONCLUSIONS
  Rapamycin displayed a potent antileukemic effect in the human Tcell leukemia cell line by inhibition of cell proliferation through G1 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.
authors: Bone Marrow Transplant Center, The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China.
authors: Yan-min
authors: YM
authors: Zhao
authors: Qian
authors: Q
authors: Zhou
authors: Yun
authors: Y
authors: Xu
authors: Xiao-yu
authors: XY
authors: Lai
authors: He
authors: H
authors: Huang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy; D012333:RNA, Messenger / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D019098:Telomerase; D020123:Sirolimus