Involvement of SRC-3 in deguelin-induced apoptosis in Jurkat cells.
The aim of the study was to investigate the anticancer effects and the molecular mechanisms of deguelin on Jurkat cells. Cell viability was assessed by MTT assay. Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay and transmission electron microscopy were used to detect cell apoptosis. A propidium iodide method was used to study cell cycle distribution. RT-PCR and Western blotting were employed to assess the expression levels of steroid receptor coactivator-3 (SRC-3), nuclear factor-kappaB (NF-kappaB) and some apoptosis related genes, including Bcl-2 and Bcl-xL. Deguelin was able to inhibit cell proliferation by a cell-cycle arrest in the G(1)/G(0) phase and induce apoptosis in Jurkat cells in vitro, with a 24-h IC(50) value of 43.73 +/- 0.35 nmol/L. The antileukemia effect of deguelin might be correlated well with the downregulation of the expression of SRC-3 and its related transcription factor NF-kappaB, which thus influenced the expression of apoptosis related genes Bcl-2 and Bcl-xL. Deguelin presented potent effects on growth arrest and apoptosis induction in Jurkat cells in vitro via the interruption of SRC-3.
Department of Hematology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Rui
R
Li
Yan
Y
Chen
Wen-xiu
WX
Shu
Zi
Z
Chen
Wen-juan
WJ
Ke
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D051548:Histone Acetyltransferases / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000235:genetics; D056921:Nuclear Receptor Coactivator 3; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D015534:Trans-Activators; D012402:Rotenone; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; C107676:deguelin