scholarly journals The influence of the BRAF V600E mutation in thyroid cancer cell lines on the anticancer effects of 5-aminoimidazole-4-carboxamide-ribonucleoside

2011 ◽  
Vol 211 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Hyun-Jeung Choi ◽  
Tae Yong Kim ◽  
Namhyun Chung ◽  
Ji Hye Yim ◽  
Won Gu Kim ◽  
...  

5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR) is an activator of 5′-AMP-activated protein kinase (AMPK), which plays a role in the maintenance of cellular energy homeostasis. Activated AMPK inhibits the protein kinase mechanistic target of rapamycin, thereby reducing the extent of protein translation and suppressing both cell growth and cell cycle entry. Recent reports indicate that AMPK-mediated growth inhibition is achieved via an action of the RAF–MEK–ERK mitogen-activated protein kinase pathway in melanoma cells harboring the V600E mutant form of the BRAF oncogene. In this study, we investigated the anti-cancer efficacy of AICAR by measuring its effects on proliferation, apoptosis, and cell cycle progression of BRAF wild-type and V600E-mutant thyroid cancer cell lines. We also explored the mechanism underlying these effects. AICAR inhibited the proliferation of BRAF V600E-mutant thyroid cancer cell lines more strongly than was the case with wild-type cell lines. The suppressive effect of AICAR on cell proliferation was associated with increased S-phase cell cycle arrest and apoptosis. Interestingly, AICAR suppressed phosphorylation of ERK and p70S6K in BRAF V600E-mutant thyroid cancer cells, but rather increased phosphorylation in wild-type cells. Together, the results indicate that AICAR-induced AMPK activation in BRAF V600E-mutant thyroid cancer cell lines resulted in increases in apoptosis and S-phase arrest via downregulation of ERK and p70S6K activity. Thus, regulation of AMPK activity may be potentially useful as a therapy for thyroid cancer if the cancer harbors a BRAF V600E mutation.

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
B Trojanowicz ◽  
Z Chen ◽  
J Bialek ◽  
Y Radestock ◽  
S Hombach-Klonisch ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Mario Rotondi ◽  
Francesca Coperchini ◽  
Oriana Awwad ◽  
Patrizia Pignatti ◽  
Christian A. Di Buduo ◽  
...  

CXCL8 displays several tumor-promoting effects. Targeting and/or lowering CXCL8 concentrations within the tumor microenvironment would produce a therapeutic benefit. Aim of this study was to test the effect of IFNγon the basal and TNFα-stimulated secretion of CXCL8 in TCP-1 and BCPAP thyroid cancer cell lines (harboring RET/PTC rearrangement and BRAF V600e mutation, resp.). Cells were incubated with IFNγ(1, 10, 100, and 1000 U/mL) alone or in combination with TNF-α(10 ng/mL) for 24 hours. CXCL8 and CXCL10 concentrations were measured in the cell supernatants. IFNγinhibited in a dose-dependent and significant manner both the basal (ANOVAF: 22.759;p<0.00001) and the TNFα-stimulated (ANOVAF: 15.309;p<0.00001) CXCL8 secretions in BCPAP but not in TPC-1 cells (NS). On the other hand, IFNγand IFNγ+ TNF-αinduced a significant secretion of CXCL10 in both BCPAP (p<0.05) and TPC-1 (p<0.05) cells. Transwell migration assay showed that (i) CXCL8 increased cell migration in both TPC-1 and BCPAP cells; (ii) IFNγsignificantly reduced the migration only of BCPAP cells; and (iii) CXCL8 reverted the effect of IFNγ. These results constitute the first demonstration that IFNγinhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line.


2019 ◽  
Vol 25 (10) ◽  
pp. 3141-3151 ◽  
Author(s):  
Iñigo Landa ◽  
Nikita Pozdeyev ◽  
Christopher Korch ◽  
Laura A. Marlow ◽  
Robert C. Smallridge ◽  
...  

2015 ◽  
Vol 6 (2-3) ◽  
pp. 87-99 ◽  
Author(s):  
Jennifer A. Morrison ◽  
Laura A. Pike ◽  
Greg Lund ◽  
Qiong Zhou ◽  
Brittelle E. Kessler ◽  
...  

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