Mensacarcin
目录号 : GC47620
A bacterial metabolite with anticancer activity
Cas No.:808750-39-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mensacarcin is a bacterial metabolite that has been found in S. bottropensis and has anticancer activity.1,2 It is cytostatic in the NCI-60 panel of cancer cell lines (mean IC50 = 1.3 µM) and cytotoxic to HepG2, HM02, KATO III, and MCF-7 cells (IC50s = 0.4-50 µM).1 Mensacarcin induces apoptosis in SK-MEL-28 and SK-MEL-5 melanoma cells.2
1.Maier, S., PflÜger, T., Loesgen, S., et al.Insights into the bioactivity of mensacarcin and epoxide formation by MsnO8Chembiochem15(5)749-756(2014) 2.Plitzko, B., Kaweesa, E.N., and Loesgen, S.The natural product mensacarcin induces mitochondrial toxicity and apoptosis in melanoma cellsJ. Biol. Chem.292(51)21102-21116(2017)
| Cas No. | 808750-39-2 | SDF | |
| Canonical SMILES | CO[C@@H]1[C@@]23[C@](C(C4=CC=CC(OC)=C41)=O)([C@@H]([C@@H]([C@](O)([C@@H]3O)C([C@H]5[C@@H](O5)C)=O)C)O)O2 | ||
| 分子式 | C21H24O9 | 分子量 | 420.4 |
| 溶解度 | DMSO: soluble,Methanol: soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3787 mL | 11.8934 mL | 23.7869 mL |
| 5 mM | 0.4757 mL | 2.3787 mL | 4.7574 mL |
| 10 mM | 0.2379 mL | 1.1893 mL | 2.3787 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Measurement of Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) in Culture Cells for Assessment of the Energy Metabolism
Bio Protoc 2018 May 20;8(10):e2850.PMID:34285967DOI:10.21769/BioProtoc.2850.
Mammalian cells generate ATP by mitochondrial (oxidative phosphorylation) and non-mitochondrial (glycolysis) metabolism. Cancer cells are known to reprogram their metabolism using different strategies to meet energetic and anabolic needs ( Koppenol et al., 2011 ; Zheng, 2012). Additionally, each cancer tissue has its own individual metabolic features. Mitochondria not only play a key role in energy metabolism but also in cell cycle regulation of cells. Therefore, mitochondria have emerged as a potential target for anticancer therapy since they are structurally and functionally different from their non-cancerous counterparts (D'Souza et al., 2011). We detail a protocol for measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measurements in living cells, utilizing the Seahorse XF24 Extracellular Flux Analyzer (Figure 1). The Seahorse XF24 Extracellular Flux Analyzer continuously measures oxygen concentration and proton flux in the cell supernatant over time ( Wu et al., 2007 ). These measurements are converted in OCR and ECAR values and enable a direct quantification of mitochondrial respiration and glycolysis. With this protocol, we sought to assess basal mitochondrial function and mitochondrial stress of three different cancer cell lines in response to the cytotoxic test lead compound Mensacarcin in order to investigate its mechanism of action. Cells were plated in XF24 cell culture plates and maintained for 24 h. Prior to analysis, the culture media was replaced with unbuffered DMEM pH 7.4 and cells were then allowed to equilibrate in a non-CO2 incubator immediately before metabolic flux analysis using the Seahorse XF to allow for precise measurements of Milli-pH unit changes. OCR and ECAR were measured under basal conditions and after injection of compounds through drug injection ports. With the described protocol we assess the basic energy metabolism profiles of the three cell lines as well as key parameters of mitochondrial function in response to our test compound and by sequential addition of mitochondria perturbing agents oligomycin, FCCP and rotenone/antimycin A. Figure 1.Overview of seahorse experiment.
The natural product Mensacarcin induces mitochondrial toxicity and apoptosis in melanoma cells
J Biol Chem 2017 Dec 22;292(51):21102-21116.PMID:29074620DOI:10.1074/jbc.M116.774836.
Mensacarcin is a highly oxygenated polyketide that was first isolated from soil-dwelling Streptomyces bacteria. It exhibits potent cytostatic properties (mean of 50% growth inhibition = 0.2 μm) in almost all cell lines of the National Cancer Institute (NCI)-60 cell line screen and relatively selective cytotoxicity against melanoma cells. Moreover, its low COMPARE correlations with known standard antitumor agents indicate a unique mechanism of action. Effective therapies for managing melanoma are limited, so we sought to investigate Mensacarcin's unique cytostatic and cytotoxic effects and its mode of action. By assessing morphological and biochemical features, we demonstrated that Mensacarcin activates caspase-3/7-dependent apoptotic pathways and induces cell death in melanoma cells. Upon Mensacarcin exposure, SK-Mel-28 and SK-Mel-5 melanoma cells, which have the BRAFV600E mutation associated with drug resistance, showed characteristic chromatin condensation as well as distinct poly(ADP-ribose)polymerase-1 cleavage. Flow cytometry identified a large population of apoptotic melanoma cells, and single-cell electrophoresis indicated that Mensacarcin causes genetic instability, a hallmark of early apoptosis. To visualize Mensacarcin's subcellular localization, we synthesized a fluorescent Mensacarcin probe that retained activity. The natural product probe was localized to mitochondria within 20 min of treatment. Live-cell bioenergetic flux analysis confirmed that Mensacarcin disturbs energy production and mitochondrial function rapidly. The subcellular localization of the fluorescently labeled Mensacarcin together with its unusual metabolic effects in melanoma cells provide evidence that Mensacarcin targets mitochondria. Mensacarcin's unique mode of action suggests that it may be a useful probe for examining energy metabolism, particularly in BRAF-mutant melanoma, and represent a promising lead for the development of new anticancer drugs.
Insights into the bioactivity of Mensacarcin and epoxide formation by MsnO8
Chembiochem 2014 Mar 21;15(5):749-56.PMID:24554499DOI:10.1002/cbic.201300704.
Mensacarcin, a potential antitumour drug, is produced by Streptomyces bottropensis. The structure consists of a three-membered ring system with many oxygen atoms. Of vital importance in this context is an epoxy moiety in the side chain of Mensacarcin. Our studies with different Mensacarcin derivatives have demonstrated that this epoxy group is primarily responsible for the cytotoxic effect of Mensacarcin. In order to obtain further information about this epoxy moiety, inactivation experiments in the gene cluster were carried out to identify the epoxy-forming enzyme. Therefore the cosmid cos2, which covers almost the complete type II polyketide synthase (PKS) gene cluster, was heterologously expressed in Streptomyces albus. This led to production of didesmethylmensacarcin, due to the fact that methyltransferase genes are missing in the cosmid. Further gene inactivation experiments on this cosmid showed that MsnO8, a luciferase-like monooxygenase, introduces the epoxy group at the end of the biosynthesis of Mensacarcin. In addition, the protein MsnO8 was purified, and its crystal structure was determined to a resolution of 1.80 Å.
Functional characterization of different ORFs including luciferase-like monooxygenase genes from the Mensacarcin gene cluster
Chembiochem 2015 May 26;16(8):1175-82.PMID:25907804DOI:10.1002/cbic.201500048.
The biologically active compound Mensacarcin is produced by Streptomyces bottropensis. The cosmid cos2 contains a large part of the Mensacarcin biosynthesis gene cluster. Heterologous expression of this cosmid in Streptomyces albus J1074 led to the production of the intermediate didesmethylmensacarcin (DDMM). In order to gain more insights into the biosynthesis, gene inactivation experiments were carried out by λ-Red/ET-mediated recombination, and the deletion mutants were introduced into the host S. albus. In total, 23 genes were inactivated. Analysis of the metabolic profiles of the mutant strains showed the complete collapse of DDMM biosynthesis, but upon overexpression of the SARP regulatory gene msnR1 in each mutant new intermediates were detected. The compounds were isolated, and their structures were elucidated. Based on the results the specific functions of several enzymes were determined, and a pathway for Mensacarcin biosynthesis is proposed.
Towards a total synthesis of the new anticancer agent Mensacarcin: synthesis of the carbocyclic core
Chemistry 2004 Oct 11;10(20):5233-42.PMID:15372645DOI:10.1002/chem.200400342.
A synthesis of the carbocyclic core associated with the new anticancer agent Mensacarcin (1) is reported. The strategy involves the synthesis of several novel highly substituted aromatic compounds, such as 12 and 23. The lithium derivative of 12 readily engages in a nucleophilic addition to benzaldehyde 4 to provide the diphenylcarbinol rac-15. The analogous benzyl ether rac-16 undergoes an intramolecular Heck reaction to provide the required tetrahydroanthracene rac-17, which can be transformed into the key tricyclic methyl ether rac-20. In a second approach, the lithium derivative of 21 is added to the hexasubstituted benzaldehyde 23 to give the diphenylcarbinol rac-35. Subsequent methylation to rac-36 followed by an intramolecular Heck reaction provides tricycle rac-37. Similarly, the oxidised compound 40 provides an electronically more suitable intramolecular Heck partner to afford compound 41. Further transformations of these substrates leads to rac-43, which incorporates the core structure of Mensacarcin (1).