ArticleThe Journal of steroid biochemistry and molecular biology2016
Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination.
Article in The Journal of steroid biochemistry and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 40 citations in OpenAlex.
- New insights into the interaction between m6A modification and lncRNA in cancer drug resistance.Cell proliferation · 2024Review
- Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis.Journal of translational medicine · 2022Article
- Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination.The Journal of steroid biochemistry and molecular biology · 2020Article
- Participation of vitamin D-upregulated protein 1 (TXNIP)-ASK1-JNK1 signalosome in the enhancement of AML cell death by a post-cytotoxic differentiation regimen.The Journal of steroid biochemistry and molecular biology · 2019Article
- Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties.Molecular cancer therapeutics · 2019Article
- JNK1 as a signaling node in VDR-BRAF induction of cell death in AML.The Journal of steroid biochemistry and molecular biology · 2018Article
- The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia.Nature communications · 2017Article
- BRAF signals to pro-apoptotic BIM to enhance AraC cytotoxicity induced in AML cells by Vitamin D-based differentiation agents.The Journal of steroid biochemistry and molecular biology · 2017Article
- The role of VDR and BIM in potentiation of cytarabine-induced cell death in human AML blasts.Oncotarget · 2016Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Arabinocytosine (AraC, also known as cytarabine) is one of the mainstays of AML therapy, but like other DNA damaging therapeutic agents it is rarely curative by itself. There is an emerging realization that the therapeutic outcomes may be improved by combining AraC with other compounds. Here we report that the addition of a differentiating agent combination immediately following AraC damage to AML blasts, selectively increases the cell kill. The experiments were performed using cultured cells from established cell lines of AML (HL60 and U937). The cells were exposed to 100nM AraC, a concentration which produced approximately 25-50% cell kill, followed by a combination of 100nM 1alpha-hydroxyvitamin D2 (1-D2) and 10μM carnosic acid (CA), which together can serve as a powerful differentiating agent combination for AML cells, but are not toxic alone. AraC-induced cell death, measured by annexin V/propidium iodide, was significantly (p<0.01) increased by the 1-D2/CA combination in both cell lines, but not by 1-D2 or CA alone. The enhancement of cell death occurred by both apoptosis and necrosis, was associated with increased DNA damage and with higher levels of DNA damage response (DDR) activated marker Chk1, but the expression of p27, a cell cycle inhibitor protein, was not enhanced by 1-D2/CA. The principal finding is that a vitamin D analog 1-D2 combined with a plant-derived antioxidant CA can markedly augment the cytotoxic action of AraC, an anti-leukemia therapeutic agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.