Protein Arginine Methyltransferase (PRMT) Inhibitors—AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures |
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| Authors: | Joanna Janisiak Patrycja Kopytko Marta Tkacz Dorota Rogi&#x;ska Magdalena Peruy&#x;ska Bogus&#x;aw Machali&#x;ski Andrzej Pawlik Maciej Tarnowski |
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| Affiliation: | 1.Department of Physiology Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (J.J.); (P.K.); (M.T.); (A.P.);2.Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland; (D.R.); (B.M.);3.Department of Experimental & Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland; |
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| Abstract: | Rhabdomyosarcoma (RMS) is a malignant soft tissue cancer that develops mostly in children and young adults. With regard to histopathology, four rhabdomyosarcoma types are distinguishable: embryonal, alveolar, pleomorphic and spindle/sclerosing. Currently, increased amounts of evidence indicate that not only gene mutations, but also epigenetic modifications may be involved in the development of RMS. Epigenomic changes regulate the chromatin architecture and affect the interaction between DNA strands, histones and chromatin binding proteins, thus, are able to control gene expression. The main aim of the study was to assess the role of protein arginine methyltransferases (PRMT) in the cellular biology of rhabdomyosarcoma. In the study we used two pan-inhibitors of PRMT, called AMI-1 and SAH, and evaluated their effects on proliferation and apoptosis of RMS cells. We observed that AMI-1 and SAH reduce the invasive phenotype of rhabdomyosarcoma cells by decreasing their proliferation rate, cell viability and ability to form cell colonies. In addition, microarray analysis revealed that these inhibitors attenuate the activity of the PI3K-Akt signaling pathway and affect expression of genes related to it. |
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| Keywords: | epigenetics RMS methyltransferases inhibitors |
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