Acta Pharm. 66 (2016) 399-410
Original research paper
PF573,228 inhibits
vascular tumor cell growth, migration as well as angiogenesis, induces
apoptosis and abrogates PRAS40 and S6RP phosphorylation
PEACE MABETA
Angiogenesis
Laboratory, Department of Anatomy and Physiology, University of Pretoria,
Private Bag X04, Tshwane, 0110, South Africa
Accepted March 4, 2016
Published online May 3,
2016
PF573,228 is a compound that targets focal adhesion kinase (FAK),
a non-receptor protein kinase, which is over-expressed in various tumors. The
aim of this study was to evaluate the effects of PF573,228
on the cells derived from mouse vascular tumors, namely, endothelioma
cells.
The
treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 µmol L–1and inhibited
cell migration with an IC50 of about 0.01 µmol L–1. Microscopic
studies revealed morphological attributes of apoptosis. These observations were
confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner,
with an IC50 of
approximately 3.7 µmol L–1 and abrogated the phosphorylation
of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array
data further revealed that PF573,228 induced caspase-3
activation, thus promoting apoptosis. Since all the processes inhibited by
PF573,228 provide important support to tumor survival
and progression, it may have a potential role in the treatment of vascular
tumors.
Keywords: PF573,228, focal adhesion kinase, endothelioma, apoptosis, angiogenesis