OAS-RNase L innate immune pathway mediates the cytotoxicity of a DNA-demethylating drug

• DOI: 10.1073/pnas.1815071116
• Publication Date: 2019-02-28T01:26:12Z
• Authors: Shuvojit Banerjee; Elona Gusho; Christina Gaughan; Beihua Dong; Xiaorong Gu; Elise Holvey-Bates; Manisha Talukdar; Yize Li; Susan R. Weiss; Frank Sicheri; Yogen Saunthararajah; George R. Stark; Robert H. Silverman
• Keywords: Azacitidine

Significance Drugs that cause epigenetic modification of DNA, such as 5-azacytidine (AZA), are used clinically to treat myelodysplastic syndromes and acute myeloid leukemia. In addition, AZA is being investigated for use against a range different types solid tumors, including lung colorectal cancers. Treatment with causes demethylation thus increasing RNA synthesis, the synthesis double-stranded RNA, which otherwise produced in virus-infected cells. We determined cell death response requires antiviral enzyme RNase L. The results identify drug target enhancing anticancer activity reducing toxicity related drugs.