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

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.