Effects of 17-AAG on the cell cycle and apoptosis of H446 cells and the associated mechanisms
Open Access
- 6 June 2016
- journal article
- Published by Spandidos Publications in Molecular Medicine Reports
- Vol. 14 (2), 1067-1074
- https://doi.org/10.3892/mmr.2016.5365
Abstract
As a heat shock protein 90 inhibitor, 17-allyl-amino-17-demethoxygeldanamycin (17-AAG) has been studied in numerous types of cancer, however the effects of 17-AAG on apoptosis and the cell cycle of H446 cells remain unclear. In the current study, the MTT method was used to evaluate the inhibitory effects of different durations and doses of 17-AAG treatment on the proliferation of H446 cells. The cells were stained with Annexin-fluorescein isothiocyanate/propidium iodide and measured by flow cytometry, and the gene and protein expression levels of signal transducer and activator of transcription 3 (STAT3), survivin, cyclin D1, cyt-C, caspase 9 and caspase 3 were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results indicated that with treatment with 1.25–20 mg/l 17-AAG for 24 and 48 h, significant inhibition of H446 cell proliferation was observed in a time- and dose-dependent manner. With treatment of 3.125, 6.25 and 12.5 mg/l 17-AAG for 48 h, significant apoptosis and cell cycle arrest was observed. The results indicated that the gene and protein expression levels of STAT3, survivin and cyclin D1 were downregulated, and cyt-C, caspase 9 and caspase 3 were upregulated by 17-AAG in a dose-dependent manner when the cells were treated with 3.125 and 6.25 mg/l 17-AAG for 48 h. The results indicated that 17-AAG is able to inhibit the cell proliferation, induce apoptosis and G2/M arrest and downregulate the gene and protein expression levels of STAT3, survivin and cyclin D1, and upregulate gene and protein expression of cyt-C, caspase 9, caspase 3.Keywords
This publication has 19 references indexed in Scilit:
- Hsp90 Inhibitors in Oncology: Ready for Prime Time?Current Oncology, 2014
- The influence of arsenic trioxide on the cell cycle, apoptosis and expression of cyclin D1 in the Jurkat cell lineActa Histochemica, 2014
- Wentilactone A as a novel potential antitumor agent induces apoptosis and G2/M arrest of human lung carcinoma cells, and is mediated by HRas-GTP accumulation to excessively activate the Ras/Raf/ERK/p53-p21 pathwayCell Death & Disease, 2013
- Survivin – biology and potential as a therapeutic target in oncologyOncoTargets and Therapy, 2013
- Targeting the molecular chaperone heat shock protein 90 (HSP90): Lessons learned and future directionsCancer Treatment Reviews, 2012
- Tanespimycin as Antitumor TherapyClinical Lymphoma Myeloma and Leukemia, 2011
- 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cellsBMC Cancer, 2010
- SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERKBlood, 2009
- 17-Allylamino-17-demethoxygeldanamycin overcomes TRAIL resistance in colon cancer cell linesBiochemical Pharmacology, 2005
- Hsp90 Inhibition Depletes Chk1 and Sensitizes Tumor Cells to Replication StressOnline Journal of Public Health Informatics, 2003