Siomycin A
(Synonyms: 盐霉素 A) 目录号 : GC44892
An inhibitor of FoxM1
Cas No.:12656-09-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
The mammalian transcription factor forkhead box M1 (FoxM1) is induced during G1 phase, with expression continuing through S phase and mitosis. Siomycin A is a peptide thiazole antibiotic, first isolated from S. sioyaensis, that interacts with the 23S rRNA of bacteria. It inhibits FoxM1 (IC50 = ~5 μM), preventing the expression of FoxM1-regulated genes, which includes FoxM1 itself. Through this mechanism, siomycin A prevents proliferation and induces apoptosis in certain types of stem cells as well as cancer cells.
| Cas No. | 12656-09-6 | SDF | |
| 别名 | 盐霉素 A | ||
| Canonical SMILES | O=C(NC(C(NC(C(N[C@@H](C)C(N[C@@]1(CCC(C2=NC(C(NC(C(NC(C(N)=O)=C)=O)=C)=O)=CS2)=N[C@]1([H])C3=CSC4=N3)C5=NC(C(NC(C(N/C(C6=NC(C(N[C@@](C7=NC8=CS7)([H])[C@@]([C@H](O)C)(O)C)=O)CS6)=C\C)=O)[C@H](O)C)=O)=CS5)=O)=O)=C)=O)=C)[C@H](C(C)C)NC9C(O)C%10=NC(C(O[C | ||
| 分子式 | C71H81N19O18S5 | 分子量 | 1648.9 |
| 溶解度 | DMF: Soluble,DMSO: 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 | 0.6065 mL | 3.0323 mL | 6.0646 mL |
| 5 mM | 0.1213 mL | 0.6065 mL | 1.2129 mL |
| 10 mM | 0.0606 mL | 0.3032 mL | 0.6065 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。
Siomycin A induces reactive oxygen species-mediated cytotoxicity in ovarian cancer cells
Oncol Lett 2021 Jun;21(6):431.PMID:33868469DOI:10.3892/ol.2021.12692.
Ovarian cancer is one of the leading causes of cancer-related death among women worldwide and accounts for 4% of all cancer cases in female patients. To date, ovarian cancer has the poorest prognosis among all types of gynecological cancer; thus, it is necessary to identify prospective therapeutic options. Previous studies have demonstrated the involvement of reactive oxygen species (ROS) in the cytotoxicity of various anticancer drugs against several types of carcinoma, including ovarian cancer. The present study aimed to investigate the anticancer effects of Siomycin A, a thiopeptide antibiotic, on the ovarian cancer cell lines PA1 and OVCAR3. To determine the viability of these cells following exposure to Siomycin A, the MTT assay was used, and apoptosis was determined by ELISA. In addition, mitochondrial membrane potential was determined by JC1 staining, and cellular ROS levels were assessed by dichlorodihydrofluorescein diacetate staining in the presence and absence of antioxidant NAC. The subsequent levels of antioxidant enzymes and glutathione were also determined following Siomycin A treatment in the two cell lines. A combination study with Siomycin A and cisplatin indicated enhanced efficiency of the drugs on ovarian cancer cell viability. The results of the present study also demonstrated that Siomycin A induced ROS production, inhibited the major antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and intracellular GSH in PA1 and OVCAR3 cells, and inhibited the cell viability with an IC50 of ~5.0 and 2.5 µM after 72 h respectively compared with the untreated controls. Additionally, the Siomycin A-induced ROS production further targeted apoptotic cell death by impairing the mitochondrial membrane potential and modulating the levels of pro- and antiapoptotic proteins compared with those in the corresponding control groups. The administration of the antioxidant N-acetylcysteine significantly abrogated the cytotoxic effects of Siomycin A. In conclusion, the results of the present study demonstrated the role of ROS in Siomycin A-mediated cytotoxicity in ovarian cancer cells.
Effects and mechanism of Siomycin A on the growth and apoptosis of MiaPaCa-2 cancer cells
Oncol Lett 2019 Sep;18(3):2869-2876.PMID:31452766DOI:10.3892/ol.2019.10633.
Siomycin A is a type of thiopeptide antibiotic that is isolated from the fermentation products of an endophytic actinomycin, which is derived from the medicinal plant Acanthopanax senticosus. The present study investigated whether Siomycin A has antitumor effects in vitro on a variety of cell lines. A Cell Counting Kit-8 assay was performed to detect the effects of Siomycin A on cell viability; morphological changes in the MiaPaCa-2 cell line were analyzed using an inverted phase contrast microscope. A Transwell migration assay was applied to detect cell migration ability. The cytoskeleton was observed by laser confocal microscopy, and apoptosis was detected using flow cytometry. A western blot assay was used to detect the expression of matrix metalloproteinase (MMP)-2, MMP-9 and α-tubulin. The results revealed that Siomycin A inhibited the proliferation of human tumor cell lines of different origins. As the concentration of Siomycin A increased, the cell density decreased gradually and cells exhibited a morphological change from spindle to spherical shape. Furthermore, 24 h after administration, the cell migration ability was inhibited. The cytoskeleton complexity and morphological changes were increased after administration of Siomycin A. The percentage of apoptotic cells was significantly increased and the expression levels of MMP-2, MMP-9 and α-tubulin were downregulated by Siomycin A. Therefore, Siomycin A was determined to effectively inhibit the proliferative ability of a variety of human tumor cell lines. Siomycin A was also determined to affect the cytoskeleton of tumor cells by downregulating the expression of α-tubulin protein.
FOXM1 inhibitor, Siomycin A, synergizes and restores 5-FU cytotoxicity in human cholangiocarcinoma cell lines via targeting thymidylate synthase
Life Sci 2021 Dec 1;286:120072.PMID:34688691DOI:10.1016/j.lfs.2021.120072.
Aims: 5-Fluorouracil (5-FU), a thymidylate synthase (TS) inhibitor, has been used as the first-line chemotherapeutic drug for cholangiocarcinoma (CCA). The side effects and drug resistance have developed the limits of the clinical application of 5-FU in CCA treatment. Upregulation of Forkhead box M1 (FOXM1) and TS were shown to play a significant role in 5-FU resistance. In this study, the effect of Siomycin A (SioA), a FOXM1 inhibitor, on enhancing 5-FU cytotoxicity and reversing 5-FU resistance in CCA cell lines were demonstrated. Main methods: Human CCA cell lines, KKU-100 and KKU-213A were used. Cell viability was determined using MTT assay. Expression of FOXM1 and TS proteins were determined using Western blotting. FOXM1 mRNA expression was quantitated using real-time PCR. The combination and dose reduction (DRI) were analyzed according to the Chou and Talalay method. Key finding: Single drug treatment of 5-FU and SioA effectively inhibited CCA cell growth in dose and time dependent fashions. The two CCA cell lines had different responses to 5-FU but exhibited similar sensitivity to SioA. FOXM1 and TS expression were increased in the 5-FU treated cells but were suppressed in the SioA treated cells. A direct binding of SioA, to TS and 5,10-methylene-tetrahydrofolate as an inactive ternary complex was simulated. The combined treatment of 5-FU with SioA showed a synergistic effect with a high DRI and restored 5-FU sensitivity in the 5-FU resistant cells. Significance: Targeting FOXM1 using SioA in combination with 5-FU might be a strategy to overcome the 5-FU resistance in CCA.
Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway
Neuro Oncol 2011 Jun;13(6):622-34.PMID:21558073DOI:10.1093/neuonc/nor023.
Glioblastoma multiforme (GBM) is a devastating disease, and the current therapies have only palliative effect. Evidence is mounting to indicate that brain tumor stem cells (BTSCs) are a minority of tumor cells that are responsible for cancer initiation, propagation, and maintenance. Therapies that fail to eradicate BTSCs may ultimately lead to regrowth of residual BTSCs. However, BTSCs are relatively resistant to the current treatments. Development of novel therapeutic strategies that effectively eradicate BTSC are, therefore, essential. In a previous study, we used patient-derived GBM sphere cells (stemlike GBM cells) to enrich for BTSC and identified maternal embryonic leucine-zipper kinase (MELK) as a key regulator of survival of stemlike GBM cells in vitro. Here, we demonstrate that a thiazole antibiotic, Siomycin A, potently reduced MELK expression and inhibited tumor growth in vivo. Treatment of stemlike GBM cells with Siomycin A resulted in arrested self-renewal, decreased invasion, and induced apoptosis but had little effect on growth of the nonstem cells of matched tumors or normal neural stem/progenitor cells. MELK overexpression partially rescued the phenotype of siomycin A-treated stemlike GBM cells. In vivo, Siomycin A pretreatment abraded the sizes of stemlike GBM cell-derived tumors in immunodeficient mice. Treatment with Siomycin A of mice harboring intracranial tumors significantly prolonged their survival period compared with the control mice. Together, this study may be the first model to partially target stemlike GBM cells through a MELK-mediated pathway with Siomycin A to pave the way for effective treatment of GBM.
Total synthesis of Siomycin A: completion of the total synthesis
Chem Asian J 2008 Jun 2;3(6):1013-25.PMID:18464235DOI:10.1002/asia.200800033.
The total synthesis of Siomycin A (1), a representative compound of the thiostrepton family of peptide antibiotics, was achieved by incorporating the five synthetic segments A (2), B (3), C (4), D (5), and E (6). The dehydropiperidine segment A (2) was esterified with the dihydroquinoline segment C (4), and the subsequent coupling with the beta-phenylselenoalanine dipeptide segment D (5) at the segment C portion followed by lactamization between the segments A and D gave segment A-C-D (27). This was amidated with the pentapeptide segment B (3) at the segment A portion followed by one-pot cyclization (between segments A and B) and elongation (with the beta-phenylselenoalanine dipeptide segment E (6) at the segment A portion), thus furnishing Siomycin A (1).