[Celastrol down-regulates expression of P-Akt and cyclin D1 in HL-60 cells and induces apoptosis].
The aim of this study was to investigate the effect of Celastrol on induction of HL-60 cell apoptosis and its possible mechanism. The proliferative activity of HL-60 cells treated with 0.25 - 8.0 μmol/L of Celastrol for 24 - 72 hours was assayed by MTT method, the effects of Celastrol on apoptosis and cell cycle of HL-60 were detected by TUNEL staining and flow cytometry with Annexin V-FITC/PI double labeling, the expression of pAkt and cyclin D1 at protein and gene level in HL-60 cells treated with Celastrol were measured by Western blot and RT-PCR. The results showed that the Celastrol could obviously inhibit the proliferation of HL-60 cells in concentration-and time-dependent manners, the IC₅₀ value of Celastrol for 24 hours was 6.21 ± 0.242 μmol/L. The Celastrol concentration-dependently induced the apoptosis of HL-60 cells, accompanying with morphological changes of apoptotic cells, which may be related with arrest of cells in G₀/G₁ phase. The Celastrol suppressed the expression of pAkt and Cyclin D1 in HL-60 cells to a varying degree which showed obvious concentration-and time-dependent manners. It is concluded that the Celastrol inhibits the proliferation and induced the apoptosis of HL-60 cells. Its mechanism may be related with down-regulation of p-Act and cyclin D1 expressions.
Ma
Yong-Lan
YL
Department of Clinical Laboratorial Examination, Air Force 457 Hospital of PLA, Wuhan 430012, Hubei Province, China.
Yi
Hong
H
Yang
Fei-Lan
FL
Zhang
Yuan
Y
Wang
Ya
Y
Wang
Ying
Y
D017209:Apoptosis / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism*; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D053978:Pentacyclic Triterpenes; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*
C530104:CCND1 protein, human; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; C050414:celastrol