J Appl Biomed 18:143-151, 2020 | DOI: 10.32725/jab.2020.019

Sunitinib malate inhibits hemangioma cell growth and migration by suppressing focal adhesion kinase signaling

Wihan Scholtz, Peace Mabeta*
University of Pretoria, Faculty of Health Sciences, Department of Physiology, Angiogenesis Laboratory, South Africa

Sunitinib malate is a small molecule that targets multiple receptor tyrosine kinases and blocks their activity. Receptors targeted by sunitinib are implicated in tumor vascularization and are overexpressed by vascular tumors encountered in infants, namely, hemangiomas. Of note is that there is still no definitive treatment for these commonly occurring tumors of infancy. The purpose of this study was to investigate the effects of sunitinib malate on hemangioma using endothelial cells isolated from a murine model of the neoplasm (sEnd.2). The effects of the drug on cell growth were evaluated using the crystal violet assay and flow cytometry, while the scratch assay was employed to measure cell migration. Proteins associated with cell migration and angiogenesis were detected using western blotting. Sunitinib was investigated further to determine its effects on the production of reactive oxygen species, a parameter associated with the promotion of neovascularization in tumors. The results showed that sunitinib significantly reduced the growth of sEnd.2 cells by causing the cells to accumulate in the sub-G1 phase of the cell cycle, and also induced a significant decrease in the migration of these hemangioma cells (P < 0.05). The western blot assay showed a decrease in the expression of adhesion proteins, focal adhesion kinase and paxillin at IC50 doses, although the expression of cadherin did not change significantly (P < 0.05). In addition, transforming growth factor-β1 (TGF-β1) expression was decreased in sunitinib-treated cells at the same dose. The adhesion proteins as well as TGF-β1 regulate cell movement and have been implicated in tumor progression. Thus, sunitinib malate may have potential in the treatment of hemangiomas.

Keywords: Angiogenesis; Focal adhesion kinase; Hemangioma; Migration; Sunitinib
Grants and funding:

The authors acknowledge funding support from the National Research Foundation (Dr. Mabeta-Project 114403) and the University of Pretoria, South Africa. We thank Prof. P. Becker for the study design and for statistical support.

Conflicts of interest:

The authors declare no conflict of interests.

Received: June 9, 2020; Revised: November 25, 2020; Accepted: December 3, 2020; Prepublished online: December 7, 2020; Published: December 14, 2020  Show citation

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Scholtz W, Mabeta P. Sunitinib malate inhibits hemangioma cell growth and migration by suppressing focal adhesion kinase signaling. J Appl Biomed. 2020;18(4):143-151. doi: 10.32725/jab.2020.019. PubMed PMID: 34907767.
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