Vitamin C Promotes Anti-Leukemia of DZNep in Acute Myeloid Leukemia

Abstract

The epigenetic treatment by 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, shows great potential to treat acute myeloid leukemia (AML). However, the variant sensitivity and incomplete response to DZNep are very common in different AML cell lines as well as primary leukemia cells from AML patients. Here, we reveal that vitamin C (Vc) dramatically promotes DZNep response in leukemia cells from different AML cell lines and primary AML patient. Vc enhances apoptosis and differentiation induced by DZNep in different AML cell lines in vitro and reduces leukemia progression in vivo. At the molecular level, Vc promotes downregulation of D-3-phosphoglycerate dehydrogenase (PHGDH), an enzyme for serine synthesis, and other anti-apoptotic genes, such as BCL2. Over-expression of PHGDH reverses the enhancing effect of Vc on the anti-leukemia effect of DZNep in AML cells. Together, our findings provide an effective approach to reduce the epigenetic treatment resistance by Vc and would be valuable in potential applications. Funding Information: This work was supported by the National Natural Science Foundation of China (81700149), Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515010199), and the Fundamental Research Funds for the Central Universities (No. 20ykpy30). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All samples were collected after obtaining informed consent in accordance with the Declaration of Helsinki. The study was approved by the ethics committees of the Institutional Review Boards. All animal experiments were performed according to protocols approved by the institutional animal care and use committee.