ArticleMolecular & cellular proteomics : MCP2012
5-Aza-2'-deoxycytidine induced growth inhibition of leukemia cells through modulating endogenous cholesterol biosynthesis.
Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- A Tutorial Review of Labeling Methods in Mass Spectrometry-Based Quantitative Proteomics.ACS measurement science au · 2024Review
- Effect of 5-Aza-2'-deoxycytidine on T-cell acute lymphoblastic leukemia cell biological behaviors and PTEN expression.CytoJournal · 2024Article
- The RORɣ/SREBP2 pathway is a master regulator of cholesterol metabolism and serves as potential therapeutic target in t(4;11) leukemia.Oncogene · 2024Article
- Targeting of Mevalonate-Isoprenoid Pathway in Acute Myeloid Leukemia Cells by Bisphosphonate Drugs.Biomedicines · 2022Review
- Roles of Farnesyl-Diphosphate Farnesyltransferase 1 in Tumour and Tumour Microenvironments.Cells · 2020Review
- The role of cholesterol metabolism in leukemia.Blood science (Baltimore, Md.) · 2019Review
- Toxic effects of phytol and retinol on human glioblastoma cells are associated with modulation of cholesterol and fatty acid biosynthetic pathways.Journal of neuro-oncology · 2018Article
- Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562.Oncotarget · 2017Article
- SILAC-Based Quantitative Proteomic Analysis Unveils Arsenite-Induced Perturbation of Multiple Pathways in Human Skin Fibroblast Cells.Chemical research in toxicology · 2017Article
- Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities.Clinical epigenetics · 2017Review
- Comparative Proteomic Study of Fatty Acid-treated Myoblasts Reveals Role of Cox-2 in Palmitate-induced Insulin Resistance.Scientific reports · 2016Article
- Five-aza-2'-deoxycytidine-induced hypomethylation of cholesterol 25-hydroxylase gene is responsible for cell death of myelodysplasia/leukemia cells.Scientific reports · 2015Article
- α-N-methylation of damaged DNA-binding protein 2 (DDB2) and its function in nucleotide excision repair.The Journal of biological chemistry · 2014Article
- Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts.Toxicology and applied pharmacology · 2014Article
- Cd²⁺-induced alteration of the global proteome of human skin fibroblast cells.Journal of proteome research · 2014Article
- Identification of novel α-n-methylation of CENP-B that regulates its binding to the centromeric DNA.Journal of proteome research · 2013Article
- Quantitative proteomic analysis revealed N'-nitrosonornicotine-induced down-regulation of nonmuscle myosin II and reduced cell migration in cultured human skin fibroblast cells.Journal of proteome research · 2013Article
- The DN2 Myeloid-T (DN2mt) Progenitor is a Target Cell for Leukemic Transformation by the TLX1 Oncogene.Journal of bone marrow research · 2013Article
- Comparison of the dipeptidyl peptidase-4 gene methylation levels between severely obese subjects with and without the metabolic syndrome.Diabetology & metabolic syndrome · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
5-Aza-2'-deoxycytidine (5-Aza-CdR), a nucleoside analog that can inhibit DNA cytosine methylation, possesses potent antitumorigenic activities for myeloid disorders. Although 5-Aza-CdR is known to be incorporated into DNA and inhibit DNA (cytosine-5)-methyltransferases, the precise mechanisms underlying the drug's antineoplastic activity remain unclear. Here we utilized a mass spectrometry-based quantitative proteomic method to analyze the 5-Aza-CdR-induced perturbation of protein expression in Jurkat-T cells at the global proteome scale. Among the ≈ 2780 quantified proteins, 188 exhibited significant alteration in expression levels upon a 24-hr treatment with 5 μm 5-Aza-CdR. In particular, we found that drug treatment led to substantially reduced expression of farnesyl diphosphate synthase (FDPS) and farnesyl diphosphate farnesyltransferase (FDFT1), two important enzymes involved in de novo cholesterol synthesis. Consistent with this finding, 5-Aza-CdR treatment of leukemia (Jurkat-T, K562 and HL60) and melanoma (WM-266-4) cells led to a marked decrease in cellular cholesterol content and pronounced growth inhibition, which could be rescued by externally added cholesterol. Exposure of these cells to 5-Aza-CdR also led to epigenetic reactivation of dipeptidyl peptidase 4 (DPP4) gene. Additionally, suppression of DPP4 expression with siRNA induced elevated protein levels of FDPS and FDFT1, and increased cholesterol biosynthesis in WM-266-4 cells. Together, the results from the present study revealed, for the first time, that 5-Aza-CdR exerts its cytotoxic effects in leukemia and melanoma cells through epigenetic reactivation of DPP4 gene and the resultant inhibition of cholesterol biosynthesis in these cells.
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