Arginine methyltransferase inhibitor-1 inhibits sarcoma viability in vitro and in vivo

  • Oncol Lett. 2018 Aug;16(2):2161-2166. doi: 10.3892/ol.2018.8929.
Baolai Zhang  1  2 ,  Xue Chen  1  2 ,  Suyin Ge  1  2 ,  Caili Peng  3 ,  Su Zhang  1  2 ,  Xu Chen  1  2 ,  Tao Liu  1  2 ,  Wenkai Zhang  1  2
Affiliations
  • 1. Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
  • 2. Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
  • 3. Day-Care Unit, Gansu Provincial People's Hospital, Lanzhou, Gansu 730000, P.R. China.
PMID: 30008914 DOI: 10.3892/ol.2018.8929
Abstract

Protein arginine methyltransferases (PRMTs) are a class of epigenetic modified Enzymes that are overexpressed in a various types of Cancer and serve pivotal functions in malignant transformation. Arginine methyltransferase inhibitor-1 (AMI-1) is a symmetrical sulfonated urea that inhibits the activity of type I PRMT in vitro. However, previous studies demonstrated that AMI-1 may also inhibit the activity of type II PRMT5 in vitro. To the best of our knowledge, the present study provides the first evidence that AMI-1 may significantly inhibit the viability of mouse sarcoma 180 (S180) and human osteosarcoma U2OS cells. Additionally, the results demonstrated that AMI-1 downregulated the activities of PRMT5, the symmetric dimethylation of histone 4 and histone 3 (a PRMT5-specific epigenetic MARK) in a mouse xenograft model of S180 and induced Apoptosis in S180 cells. Taken together, the results suggest that AMI-1 may exhibit antitumor effects against sarcoma cells by targeting PRMT5.

Keywords
arginine methyltransferase inhibitor 1; histone methylation; protein arginine methyltransferase 5; sarcoma; symmetric dimethylation of histone 3; symmetric dimethylation of histone 4.
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