The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line

2016 ◽  
Vol 34 (5) ◽  
pp. 531-540 ◽  
Author(s):  
Raffaele Pezzani ◽  
Beatrice Rubin ◽  
Loris Bertazza ◽  
Marco Redaelli ◽  
Susi Barollo ◽  
...  
Author(s):  
Tuğçe Balcı Okcanoğlu ◽  
Çağla Kayabaşı ◽  
Cumhur Gündüz

Long non-coding RNAs (lncRNAs) are involved in a range of biological processes, such as cellular differentiation, migration, apoptosis, invasion, proliferation, and transcriptional regulation. The aberrant expression of lncRNAs plays a significant role in several cancer types. Aurora kinases are increasingly expressed in various malignancies; accordingly, the inhibition of these enzymes may represent a novel approach for the treatment of various cancers. CCT137690, an Aurora kinase inhibitor, displays an anti-proliferative activity in human cancer cell lines. The aim of the present study was to investigate the anti-proliferative and cytotoxic effects of CCT137690 on estrogen receptor (ER)-positive human breast cancer cell line (MCF-7) and ER-negative human breast cancer cell line (MDA-MB-231). In addition, this study was targeted toward determining the changes induced in lncRNA expression levels following the initiation of Aurora kinase inhibitor treatment. The cytotoxic effects of CCT137690 were determined by means of the xCELLigence system. Furthermore, the anti-proliferative role of CCT137690 in breast cancer was investigated by checking the changes in lncRNA expression profiles using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The half-maximal inhibitory concentrations (IC50) of CCT137690 were determined as 4.5 μM (MCF-7) and 7.27 μM (MDA-MB-231). Several oncogenic lncRNAs (e.g., PRINS, HOXA1AS, and NCRMS) were downregulated in both ER-negative and ER-positive cell lines. On the other hand, tumor suppressor lncRNAs (e.g., DGCR5 and IGF2AS) were upregulated in the ER-positive cell line. After CCT137690 treatment, HOXA11AS and PCAT-14 lncRNAs were downregulated in the ER-positive cell lines. In addition, MER11C, SCA8, BC200, HOTAIR, PCAT-1, UCA1, SOX2OT, and HULC lncRNAs were downregulated in the ER-negative cell lines. The results of the present study indicated that Aurora kinase inhibitor CCT137690 could be a potential anti-cancer agent for breast cancer treatment.


2017 ◽  
Vol 28 (6) ◽  
pp. 634-644 ◽  
Author(s):  
Kleiton S. Borges ◽  
Augusto F. Andrade ◽  
Vanessa S. Silveira ◽  
David S. Marco Antonio ◽  
Elton J.R. Vasconcelos ◽  
...  

2018 ◽  
Vol 65 (4) ◽  
pp. 444-455 ◽  
Author(s):  
Ali Zekri ◽  
Yashar Mesbahi ◽  
Elham Boustanipour ◽  
Zahra Sadr ◽  
Seyed H. Ghaffari

2013 ◽  
Vol 62 ◽  
pp. 777-784 ◽  
Author(s):  
Stefan O. Ochiana ◽  
Vidya Pandarinath ◽  
Zhouxi Wang ◽  
Rishika Kapoor ◽  
Mary Jo Ondrechen ◽  
...  

2013 ◽  
Vol 9 (3) ◽  
pp. 215-224 ◽  
Author(s):  
M. Mita ◽  
M. Gordon ◽  
N. Rejeb ◽  
A. Gianella-Borradori ◽  
V. Jego ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1498-1505 ◽  
Author(s):  
Jürgen den Hollander ◽  
Sara Rimpi ◽  
Joanne R. Doherty ◽  
Martina Rudelius ◽  
Andreas Buck ◽  
...  

Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function.


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