Zhang Baolai, Chen Xue, Ge Suyin, Peng Caili, Zhang Su, Chen Xu, Liu Tao, Zhang Wenkai
Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Oncol Lett. 2018 Aug;16(2):2161-2166. doi: 10.3892/ol.2018.8929. Epub 2018 Jun 8.
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 . However, previous studies demonstrated that AMI-1 may also inhibit the activity of type II PRMT5 . 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.
蛋白质精氨酸甲基转移酶（PRMTs）是一类表观遗传修饰酶，在多种癌症中过度表达，并在恶性转化中发挥关键作用。精氨酸甲基转移酶抑制剂-1（AMI-1）是一种对称磺化尿素，可抑制I型PRMT的活性。然而，先前的研究表明，AMI-1也可能抑制II型PRMT5的活性。据我们所知，本研究首次提供证据表明，AMI-1可能显著抑制小鼠肉瘤180（S180）和人骨肉瘤U2OS细胞的活力。此外，结果表明，在S180小鼠异种移植模型中，AMI-1下调了PRMT5的活性、组蛋白4和组蛋白3的对称二甲基化（一种PRMT5特异性表观遗传标记），并诱导S180细胞凋亡。综上所述，结果表明AMI-1可能通过靶向PRMT5对肉瘤细胞发挥抗肿瘤作用。
