Functional assays, such as flow cytometry, cytotoxicity assays and ELISA, were performed to determine the demethylation agent, decitabine (5-aza-2'-deoxycytidine, DAC)-treated cancer cell improved antigen specific T cells response.
Together, these experiments provide preclinical evidence that the FDA-approved DNA methylation inhibitor DAC may be repurposed to treat patients with osteosarcoma based on its efficacy to decrease proliferation, to induce osteoblast differentiation, and to reduce metastasis to visceral organs.<b>Significance:</b> These findings describe the effects of DNA methyltransferase inhibition on ERα and its potential role as a tumor suppressor in osteosarcoma.<i>See related commentary by Roberts, p. 1034</i><i>See related article by El Ayachi and colleagues; Cancer Res 79(5);982-93</i>.
The HMAs 5-azacitidine (AZA) and 2'-deoxy-5-azacitidine (decitabine, DAC) inhibit DNA methylation and have shown significant clinical benefits in patients with myeloid malignancies.