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The Aplidin analogs PM01215 and PM02781 inhibit angiogenesis in vitro and in vivo

Overview of attention for article published in BMC Cancer, October 2015
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Title
The Aplidin analogs PM01215 and PM02781 inhibit angiogenesis in vitro and in vivo
Published in
BMC Cancer, October 2015
DOI 10.1186/s12885-015-1729-4
Pubmed ID
Authors

Bojana Borjan, Normann Steiner, Silvia Karbon, Johann Kern, Andrés Francesch, Martin Hermann, Wolfgang Willenbacher, Eberhard Gunsilius, Gerold Untergasser

Abstract

Novel synthesized analogs of Aplidin, PM01215 and PM02781, were tested for antiangiogenic effects on primary human endothelial cells in vitro and for inhibition of angiogenesis and tumor growth in vivo. Antiangiogenic activity of both derivatives was evaluated by real-time cell proliferation, capillary tube formation and vascular endothelial growth factor (VEGF)-induced spheroid sprouting assays. Distribution of endothelial cells in the different phases of the cell cycle was analyzed by flow cytometry. Aplidin analogs were tested in vivo in chicken chorioallantoic membrane (CAM) assays. Both derivatives inhibited angiogenic capacities of human endothelial cells (HUVECs) in vitro at low nanomolar concentrations. Antiangiogenic effects of both analogs were observed in the CAM. In addition, growth of human multiple myeloma xenografts in vivo in CAM was significantly reduced after application of both analogs. On the molecular level, both derivatives induced cell cycle arrest in G1 phase. This growth arrest of endothelial cells correlated with induction of the cell cycle inhibitor p16(INK4A) and increased senescence-associated beta galactosidase activity. In addition, Aplidin analogs induced oxidative stress and decreased production of the vascular maturation factors Vasohibin-1 and Dickkopf-3. From these findings we conclude that both analogs are promising agents for the development of antiangiogenic drugs acting independent on classical inhibition of VEGF signaling.

Mendeley readers

The data shown below were compiled from readership statistics for 7 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 7 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 2 29%
Student > Master 1 14%
Student > Bachelor 1 14%
Student > Ph. D. Student 1 14%
Lecturer 1 14%
Other 1 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 29%
Psychology 2 29%
Agricultural and Biological Sciences 2 29%
Medicine and Dentistry 1 14%