Mithramycin A
(Synonyms: 光辉霉素,Mithramycin A) 目录号 : GC15060Mithramycin A是一种从S. grieseus中分离出来的抗生素。作为特异性蛋白1（Sp1）的选择性抑制剂，Mithramycin A与富含GC的DNA序列结合，取代与癌基因启动子结合的Sp1转录因子，抑制基因表达。
Cas No.:18378-89-7
Sample solution is provided at 25 µL, 10mM.
Mithramycin A is an antibiotic isolated from S. grieseus [1]. As a selective inhibitor of specific protein 1 (Sp1), Mithramycin A binds to DNA sequences rich in GC, replacing the Sp1 transcription factor that binds to oncogenes, thereby inhibiting gene expression [2]. Mithramycin A has anti-tumor and neuroprotective effects [3].
In vitro, Mithramycin A (0-400nM, 24 hours) can dose-dependently inhibit the expression of GSTM2 protein in BFTC 905 and 5637 cells [4]. Mithramycin A (75μM; 24 hours) significantly increases the apoptosis of TNF-induced TF-1 cells, and the enhanced cytotoxicity of Mithramycin A on TNF occurs at the FADD level or its downstream position [5].
In vivo, Mithramycin A (0.2mg/kg/day; three times per week for 29 days; i.p.) significantly reduces the tumor volume of human cervical cancer cell xenograft mice and increases the number of TUNEL-positive cells in the tumor xenografts [6]. Mithramycin A (150μg/kg/day; 60 days; i.p.) treatment can effectively inhibit the Sp1 activation level in APPswe/PS1dE9 mice, significantly reduce the Aβ level and plaque load in the mouse brain, and reduce tau hyperphosphorylation, and increase synaptic markers [7].
References:
[1] Sleiman SF, Berlin J, Basso M, Karuppagounder SS, Rohr J, Ratan RR. Histone Deacetylase Inhibitors and Mithramycin A Impact a Similar Neuroprotective Pathway at a Crossroad between Cancer and Neurodegeneration. Pharmaceuticals (Basel). 2011;4(8):1183-1195.
[2] Choi ES, Nam JS, Jung JY, Cho NP, Cho SD. Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer. Sci Rep. 2014;4:7162.
[3] Sleiman SF, Langley BC, Basso M, et al. Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration. J Neurosci. 2011;31(18):6858-6870.
[4] Shen CH, Wu JY, Wang SC, et al. The suppressive role of phytochemical-induced glutathione S-transferase Mu 2 in human urothelial carcinoma cells. Biomed Pharmacother. 2022;151:113102.
[5] Duverger V, Murphy AM, Sheehan D, et al. The anticancer drug mithramycin A sensitises tumour cells to apoptosis induced by tumour necrosis factor (TNF). Br J Cancer. 2004;90(10):2025-2031.
[6] Choi ES, Nam JS, Jung JY, Cho NP, Cho SD. Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer. Sci Rep. 2014;4:7162.
[7] Wei C, Zhang W, Zhou Q, et al. Mithramycin A Alleviates Cognitive Deficits and Reduces Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease. Neurochem Res. 2016;41(8):1924-1938.
Mithramycin A是一种从S. grieseus中分离出来的抗生素 [1]。作为特异性蛋白1（Sp1）的选择性抑制剂，Mithramycin A与富含GC的DNA序列结合，取代与癌基因启动子结合的Sp1转录因子，抑制基因表达 [2]。Mithramycin A具有抗肿瘤和神经保护作用 [3]。
在体外，Mithramycin A（0-400nM, 24h）能够剂量依赖性地抑制BFTC 905和5637细胞中GSTM2蛋白的表达 [4]。Mithramycin A（75μM; 24h）显著增加TNF诱导TF-1细胞的细胞凋亡，Mithramycin A对TNF细胞毒性的增强效应发生在FADD水平上或者在其下游位置 [5]。
在体内，Mithramycin A（0.2mg/kg/day; three times per week for 29 days; i.p.）显著降低人类宫颈癌细胞异种移植小鼠的肿瘤体积，并且增加了肿瘤异种移植物中的TUNEL阳性细胞数量[6]。Mithramycin A（150μg/kg/day; 60 days; i.p.）治疗能够有效抑制APPswe/PS1dE9小鼠的Sp1激活水平，显著降低小鼠大脑Aβ水平和斑块负荷，并且减少tau过度磷酸化，增加突触标记物 [7]。
| Cell experiment [1]: | |
Cell lines | TF-1 cells |
Preparation Method | For GM-CSF withdrawal experiments, TF-1 cells were washed twice in Hank's buffered saline solution, then resuspended in RPMI 1640 medium containing 10% FCS in the presence or absence of 75nM mithramycin. For combination experiments with TNF (20ng/ml), cells were maintained in complete medium and treated with Mithramycin A simultaneously to the different drugs. Collect the cells after 24 hours of co-culture. Cell cycle status and quantification of DNA fragmentation was performed by propidium iodide (PI) staining. DNA content was determined using a FACSCalibur flow cytometer. Quantification of apoptosis by phosphatidylserine exposure was assessed by annexin V staining using the Alexa Flour 488 kit according to the manufacturer's instruction. |
Reaction Conditions | 75μM; 24h |
Applications | Mithramycin A increased apoptosis in TNF-induced TF-1 cells. The enhanced cytotoxic effect of Mithramycin A on TNF was observed at the FADD level or at its downstream location. |
| Animal experiment [2]: | |
Animal models | Nude mouse (xenograft model) |
Preparation Method | KB cells were suspended in sterile PBS and injected subcutaneously into the right flank of mice. Mice were randomized into two groups containing five mice each and treated with 0.2mg/kg/day of Mithramycin A (i.p.) three times per week for 29 days. Control mice received an equal volume of vehicle. After 29 days, bodies, organs and tumors were weighed and tumor volumes determined. Tumors were measured along the two diameter axis with calibers to allow calculation of tumor volume. |
Dosage form | 0.2mg/kg/day; three times per week for 29 days; i.p. |
Applications | Mithramycin A significantly reduces the tumor volume in mice with human cervical cancer cell xenografts. |
References: | |
| Cas No. | 18378-89-7 | SDF | |
| 别名 | 光辉霉素,Mithramycin A | ||
| 化学名 | (1S)-5-Deoxy-1-C-[(2S,3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy--D-arabino-hexopyranosyl)--D-arabino-hexopyranosyl]oxy]-3-[(O-2,6-dideoxy-3-C-methyl--D-ribo-hexopyranosyl-(1.fwdarw.3)-O-2,6-dideoxy--D-lyxo-hexopyranosyl-(1.fwdarw.3)-2,6-dideoxy--D-arabino-hexo | ||
| Canonical SMILES | CC1C(C(CC(O1)OC2CC(OC(C2O)C)OC3=CC4=CC5=C(C(=O)C(C(C5)C(C(=O)C(C(C)O)O)OC)OC6CC(C(C(O6)C)O)OC7CC(C(C(O7)C)O)OC8CC(C(C(O8)C)O)(C)O)C(=C4C(=C3C)O)O)O)O | ||
| 分子式 | C52H76O24 | 分子量 | 1085.16 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 20 mg/ml,Ethanol: 10 mg/ml,PBS (pH 7.2): 2 mg/ml | 储存条件 | Desiccate at -20°C |
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| 1 mM | 921.5 μL | 4.6076 mL | 9.2152 mL |
| 5 mM | 184.3 μL | 921.5 μL | 1.843 mL |
| 10 mM | 92.2 μL | 460.8 μL | 921.5 μL |
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