Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition.
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.
Zhao
Yan-min
YM
Bone Marrow Transplant Center, The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China.
Zhou
Qian
Q
Xu
Yun
Y
Lai
Xiao-yu
XY
Huang
He
H
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*
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D019098:Telomerase; D020123:Sirolimus