Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells
Author
Cusimano, Antonella; Puleio, Roberto; D'Alessandro, Natale; Loria, Guido R.; McCubrey, James A.; Montalto, Giuseppe; Cervello, Melchiorre
Abstract
Hepatocellular carcinoma (HCC) is characterized by limited response to current
drug therapies. Here, we report that SC66, a novel AKT inhibitor, reduced cell viability
in a dose- and time-dependent manner, inhibited colony formation and induced
apoptosis in HCC cells. SC66 treatment led to a reduction in total and phosphoAKT levels. This was associated with alterations in cytoskeleton organization, a
reduction in expression levels of E-cadherin, β-catenin and phospho-FAK, together
with up-regulation of Snail protein levels. All these alterations were coupled with
anoikis cell death induction. In addition, SC66 induced the production of reactive
oxygen species (ROS) and DNA damage. Pre-treatment with the ROS scavenger
N-Acetyl-cysteine (NAC) prevented SC66-induced cell growth inhibition and anoikis.
SC66 significantly potentiated the effects of both conventional chemotherapeutic and
targeted agents, doxorubicin and everolimus, respectively. In vivo, SC66 inhibited
tumor growth of Hep3B cells in xenograft models, with a similar mechanism observed
in the in vitro model. Taken together, these data indicate that the AKT inhibitor SC66
had antitumor effects on HCC cells. This was mediated by ROS production, induction
of anoikis-mediated cell death and inhibition of the AKT cell survival pathway. Our
results provide a rational basis for the use of SC66 in HCC treatment.
Subject
Date
2014
Citation:
APA:
Cusimano, Antonella, & Puleio, Roberto, & D'Alessandro, Natale, & Loria, Guido R., & McCubrey, James A., & Montalto, Giuseppe, & Cervello, Melchiorre. (January 2014).
Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8136
MLA:
Cusimano, Antonella, and Puleio, Roberto, and D'Alessandro, Natale, and Loria, Guido R., and McCubrey, James A., and Montalto, Giuseppe, and Cervello, Melchiorre.
"Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells". .
. (),
January 2014.
April 29, 2024.
http://hdl.handle.net/10342/8136.
Chicago:
Cusimano, Antonella and Puleio, Roberto and D'Alessandro, Natale and Loria, Guido R. and McCubrey, James A. and Montalto, Giuseppe and Cervello, Melchiorre,
"Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells," , no.
(January 2014),
http://hdl.handle.net/10342/8136 (accessed
April 29, 2024).
AMA:
Cusimano, Antonella, Puleio, Roberto, D'Alessandro, Natale, Loria, Guido R., McCubrey, James A., Montalto, Giuseppe, Cervello, Melchiorre.
Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in hepatocellular carcinoma cells. .
January 2014;
():
.
http://hdl.handle.net/10342/8136. Accessed
April 29, 2024.
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