<abstract xmlns="http://www.w3.org/1999/xhtml"> 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-1 and 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, the drug may have a potential role in the treatment of vascular tumors.</abstract>

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-1 and 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, the drug may have a potential role in the treatment of vascular tumors.

PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

Angiogenesis Laboratory Department of Anatomy and Physiology University of Pretoria, Private Bag X04 Tshwane, 0110, South Africa

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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...

PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

Publié en ligne: 29 juin 2016

Pages: 399 - 410

Accepté: 11 janv. 2016

DOI: https://doi.org/10.1515/acph-2016-0031

Mots clés
PF573,228, focal adhesion kinase, endothelioma, apoptosis, angiogenesis

© by Peace Mabeta

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

Publié en ligne: 29 juin 2016

Pages: 399 - 410

Accepté: 11 janv. 2016

DOI: https://doi.org/10.1515/acph-2016-0031

Mots clésPF573,228, focal adhesion kinase, endothelioma, apoptosis, angiogenesis

© by Peace Mabeta

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mots clés
PF573,228, focal adhesion kinase, endothelioma, apoptosis, angiogenesis