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Mitomycin C

现货
Catalog No.
A4452
抗生素和抗肿瘤剂,抑制DNA合成
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 580.00
现货
5mg
¥ 500.00
现货
10mg
¥ 700.00
现货

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Background

Mitomycin C, a kind of antibiotic isolated from Streptomyces caespitosus or Streptomyces lavendulae, inhibits DNA synthesis through covalent mitomycin C-DNA adduct with EC50 values of 0.14μM in PC3 cells. Therefore, it was served as a chemotherapeutic agent that has demonstrated its antitumor activity and has been used widely in treatment of various cancers. [1]
Mitomycin-C enhanced TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis in p53 deficient colon cancer HCT116 cells. In the cell viability assay, pretreated with 5M with mitomycin C for 24h and then exposure to 25ng/ml TRAIL  and 5M mitomycin C for 12h in HCT116 cells showed surprisingly decreased cell viability. In the crystal violet staining assay showed 5M mitomycin C combinated 25ng/ml TRAIL can substantially enhanced suppression effects of HCT116 cells. Pretreatment with 5M mitomycin C can enhanced TRAIL initiated processing of caspase-8, -9, -3 and cleavage of RARP (poly-ADP-ribose polymerase, substrate of caspase-3).  The western blot assay showed in both HCT116 and HT29 cells, mitomycin C suppressed the expression anti apoptotic proteins Mcl-1, Bcl-2, Bcl-XL, and downregulated caspase-inhibitor c-IAP-1, XIAP, while upregulated expression of pro-apoptotic proteins Bax and Bim .[2]
The NMRI-Fox1nu nude mice was inoculated subcutaneously and then randomized to several groups: treated with electrochemotherapy and administrated 5mM mitomycin C or electrochemotherapy only or 5mM mitomycin C only. Results showed that tumor volume reduced in electrochemotherapy plus mitomycin C group, and mice survival rates were greater in electrochemotherapy plus mitomycin C group and mitomycin C group only, compared controls(p<0.001). The tumor response rate was 53% for mitomycin C alone.[3]
References:
[1] Danshiitsoodol N, de Pinho CA, Matoba Y, Kumagai T, Sugiyama M. The mitomycin C (MMC)-binding protein from MMC-producing microorganisms protects from the lethal effect of bleomycin: crystallographic analysis to elucidate the binding mode of the antibiotic to the protein. J Mol Biol (2006) 360 (2): 398–408
[2] Hairong Cheng, Bo Hong, Lanlan Zhou, Joshua E. Allen, Guihua Tai, Robin Humphreys,David T. Dicker, Yingqiu Y. Liu & Wafik S. El-Deiry. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors. Cell Cycle (2012) 11(17):3312-3323
[3] Juan Luis Vásquez, Per Ibsen, Henriette Lindberg, Julie Gehl. In Vitro and In Vivo Experiments on Electrochemotherapy for Bladder Cancer. Journal of Urology (2014)

文献引用

1. Liu TP, Hsieh YY, et al. "Systematic polypharmacology and drug repurposing via an integrated L1000-based Connectivity Map database mining." R Soc Open Sci. 2018 Nov 28;5(11):181321. PMID:30564416
2. Deng Y, Li F, et al. "Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition." Mol Carcinog. 2018 Jun;57(6):807-814. PMID:29500880
3. Meng L, Wang X, et al. "BAF53a is a potential prognostic biomarker and promotes invasion and epithelial-mesenchymal transition of glioma cells." Oncol Rep. 2017 Dec;38(6):3327-3334. PMID:290395840

Chemical Properties

Physical AppearanceA solid
StorageStore at 4°C
M.Wt334.33
Cas No.50-07-7
FormulaC15H18N4O5
SynonymsAmetycine
Solubility≥16.7mg/mL in DMSO, <2.42 mg/mL in EtOH, <2.4 mg/mL in H2O
Chemical Name((1aS,8S,8aR,8bS)-6-amino-8a-methoxy-5-methyl-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2',3':3,4]pyrrolo[1,2-a]indol-8-yl)methyl carbamate
SDFDownload SDF
Canonical SMILESNC(C1=O)=C(C)C(C2=C1[C@@H](COC(N)=O)[C@]3(OC)N2C[C@H]4[C@@H]3N4)=O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

结肠腺癌HCT116,HCT116(p53-/-)结肠癌,HT-29人结肠癌细胞,人膀胱癌细胞株SW780

溶解方法

该化合物在DMSO中的溶解度大于16.7 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应时间

1 μM, 5 μM, 10 μM, 12 h或24 h

应用

MMC显著增强TRAIL对HCT116(p53-/-)细胞增殖的抑制作用。在TRAIL抗性的HT-29细胞中,MMC增强TRAIL诱导的凋亡。MMC预处理增强了HCT116(p53-/-)细胞和HT-29细胞对莱沙可单抗和帕曲单抗的敏感性。MMC通过下调抗凋亡蛋白和上调细胞存活蛋白和TRAIL死亡受体,敏化结肠癌细胞中TRAIL诱导的凋亡。

动物实验 [1]:

动物模型

异种移植HCT116(p53-/-)结肠肿瘤和HT-29结肠肿瘤的小鼠

剂量

腹膜内注射,1 mg/kg

应用

使用联合治疗方案,每隔一天腹膜内注射1 mg/kg剂量的MMC以及静脉内注射100 μg的TRAIL,连续10次循环,显著抑制肿瘤生长,对体重无影响。

其他注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Hairong Cheng, Bo Hong, Lanlan Zhou, Joshua E. Allen, Guihua Tai, Robin Humphreys,David T. Dicker, Yingqiu Y. Liu & Wafik S. El-Deiry. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors. Cell Cycle (2012) 11(17):3312-3323.

质量控制

化学结构

Mitomycin C

相关生物数据

CORM-3

相关生物数据

CORM-3

相关生物数据

CORM-3