Cytarabine
Cytarabine (AraC), an analogue of deoxycytidine, is the most effective cytotoxic agent in the treatment of acute myeloid leukemia (AML), which blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases [1].
Cytarabine is incorporated into DNA, it blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases. The most essential step in the AraC activation is phosphorylation into the monophosphate form, which is catalyzed by deoxycytidine kinase (dCK).
In AraC-sensitive rat leukemic cells, sole expression of inactive or spliced dCK forms make a cell resistant to the cytotoxic effects of AraC. It was reported that Ara-C also causes placental growth retardation, induce apoptosis and also impair cell proliferation in the zone of placental labyrinth. By injecting Ara-C into pregnant rats, the placentas were examined from 1 to 48h. the apoptosis of trophoblastic cells in the placental labyrinth zone increased from 3 h after the injecting and then peaked at 6 h and returned to control level at 48 h. Immunoreactivity of p53 protein in the placental labyrinth zone was significantly enhanced and peaked at 3 h after treatment, while no increase in p53 mRNA expression was detected by a reverse transcription polymerase chain reaction [1, 2].
A retrospective analysis was performed in 40 patients which treated with cytarabine 1000 mg/m2/day, mitoxantrone 8 mg/m2/day and etoposide 100 mg/m2/day for five days. 30% of remission rate and 11.2 months of median remission duration was got. In univariate analysis, compared to ≥second relapse (p = 0.02), patients in first relapse had improved overall survival [3].
References:
[1].Veuger MJT, Heemskerk MHM, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. Blood, 2002, 99(4): 1373-1380.
[2].Yamauchi H, Katayama K, Ueno M, et al. Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta. Biology of Reproduction, 2004, 70(6): 1762-1767.
[3]. Liedtke M, Dunn T, Dinner S, et al. Salvage therapy with mitoxantrone, etoposide and cytarabine in relapsed or refractory acute lymphoblastic leukemia. Leukemia Research, 2014, 38(12): 1441-1445.
- 1. Yang Li, Hanying Huang, et al. "TSC22D3 as an immune-related prognostic biomarker for acute myeloid leukemia." iScience. 2023 Jul 22;26(8):107451. PMID: 37575189
- 2. Xiahong Tang, Jun Ke, et al. "Hypoxic preconditioned mesenchymal stem cells ameliorate rat brain injury after cardiopulmonary resuscitation by suppressing neuronal pyroptosis." J Cell Mol Med. 2023 Jul;27(13):1836-1858. PMID: 37246833
- 3. Jing-Ting Chiou, Chia-Chi Hsu, et al. "Cytarabine-induced destabilization of MCL1 mRNA and protein triggers apoptosis in leukemia cells." Biochem Pharmacol. 2023 May:211:115494. PMID: 36924905
- 4. Emmanuelle Supper, Saskia Rudat, et al. "Cut-like homeobox 1 (CUX1) tumor suppressor gene haploinsufficiency induces apoptosis evasion to sustain myeloid leukemia." Nat Commun. 2021 Apr 30;12(1):2482. PMID: 33931647
- 5. Zhijun Liu, Himani Nailwal, et al. "A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation." Immunity. 2021 Feb 9;54(2):247-258.e7. PMID: 33444549
- 6. Lin KH, Xie A, et al. "Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity." Cell Metab. 2019 Feb 5. pii: S1550-4131(19)30011-7. PMID: 30773463
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 243.2 |
| Cas No. | 147-94-4 |
| Formula | C9H13N3O5 |
| Solubility | insoluble in EtOH; ≥28.6 mg/mL in H2O; ≥11.73 mg/mL in DMSO |
| Chemical Name | 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one |
| SDF | Download SDF |
| Canonical SMILES | C1=CN(C(=O)N=C1N)C2C(C(C(O2)CO)O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
rat sympathetic neurons |
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Preparation method |
Limited solubility in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM |
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Applications |
Cytarabine apparently induced apoptosis of rat sympathetic neurons at 10 μM, of which 100 μM showed the highest toxicity and killed over 80% of the neurons by 84 hours, involving the release of mitochondrial cytochrome-c and the activation of caspase-3. |
| Animal experiment [2]: | |
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Animal models |
Pregnant Slc:Wistar rats |
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Dosage form |
Intraperitoneal injection, 250 mg/kg |
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Application |
Cytarabine (250 mg/kg) caused placental growth retardation and increased placental trophoblastic cells apoptosis in the placental labyrinth zone of the pregnant Slc:Wistar rats, which increases from 3 hour after the treatment and peaks at 6 hour before returning to control levels at 48 hour, with remarkably enhanced p53 protein, p53 trancriptional target genes such as p21, cyclinG1 and fas and caspase-3 activity. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Besirli C G, Deckwerth T L, Crowder R J, et al. Cytosine arabinoside rapidly activates Bax-dependent apoptosis and a delayed Bax-independent death pathway in sympathetic neurons[J]. Cell death and differentiation, 2003, 10(9): 1045. [2]. Yamauchi H, Katayama K, Ueno M, et al. Involvement of p53 in 1-β-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta[J]. Biology of reproduction, 2004, 70(6): 1762-1767. |
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