Mitomycin C
(Synonyms: 丝裂霉素 C,Ametycine) 目录号 : GC12353A potent DNA crosslinker
Sample solution is provided at 25 µL, 10mM.
| Cell experiment [1, 2]: | |
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Cell lines |
HCT116, HT-29 |
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Preparation Method |
Ten millimolar Mitomycin C is prepared in 100% dimethyl sulfoxide, stored as small aliquots at -80°C and then diluted as needed in cell culture medium. |
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Reaction Conditions |
5 μM,12 or 24h |
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Applications |
Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity. Mitomycin C not only potentiates TRAIL-induced apoptosis in HCT116 (p53−/−) colon cancer cells but also sensitizes TRAIL- resistant colon cancer cells HT-29 to the cytokine. Mitomycin C inhibits HT-29 with IC50 of 40 nM. |
| Animal experiment [1]: | |
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Animal models |
Nude mice (6 weeks) injected subcutaneously with 1 × 106 HCT116 (p53−/−) or 2 × 106 HT-29 cells mixed with Matrigel |
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Preparation Method |
Ten millimolar Mitomycin C is prepared in 100% dimethyl sulfoxide, stored as small aliquots at -80°C and then diluted as needed in cell culture medium. |
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Dosage form |
1 mg/kg, Intraperitoneal injection |
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Applications |
Mitomycin C suppresses tumor growth significantly and does not impact the weight of the mice with TRAIL, indicating that the therapeutic combination of Mitomycin C and TRAIL is well-tolerated and has anti-tumor activity in vivo. |
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References: [1]. Cheng H, et al. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors: evidence for the role of c-Jun N-terminal kinase activation. Cell Cycle. 2012 Sep 1;11(17):3312-23. [2]. Hodgkinson TJ, et al. Chemical synthesis and cytotoxicity of some azinomycin analogues devoid of the 1-azabicyclo[3.1.0]hexane subunit. Bioorg Med Chem Lett. 2000 Feb 7;10(3):239-41. |
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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.
Mitomycin C is an antibiotic that has demonstrated antitumor activity in preclinical and clinical studies and is widely used to treat various cancers. Mitomycin C is known to act synergistically with capecitabine and irinotecan. Some studies suggested that the combination of 5-FU plus Mitomycin C is more active in vitro than mono-therapy in colorectal cancer. The efficacy of the combination of Mitomycin C with other cytotoxic agents such as capecitabine and raltiterxed for colorectal cancer has been reported.[1]
Mitomycin C not only potentiates TRAIL-induced apoptosis in HCT116 (p53−/−) colon cancer cells but also sensitizes TRAIL-resistant colon cancer cells HT-29 to the cytokine. At a mechanistic level, Mitomycin C downregulates cell survival proteins, including Bcl2, Mcl-1 and Bcl-XL, and upregulates pro-apoptotic proteins including Bax, Bim and the cell surface expression of TRAIL death receptors DR4 and DR5. Besides, the result of cell experiment indicates that Mitomycin C inhibits HT-29 with IC50 of 40 nM. [1,2]
Mitomycin C also plays an effective role in antitumor in vivo. For in vivo experiment, Mitomycin C suppressed tumor growth significantly and did not impact the weight of the mice with TRAIL, indicating that the therapeutic combination of Mitomycin C and TRAIL is well-tolerated and has anti-tumor activity in vivo. [1]
References:
[1]. Cheng H, et al. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors: evidence for the role of c-Jun N-terminal kinase activation. Cell Cycle. 2012 Sep 1;11(17):3312-23.
[2]. Hodgkinson TJ, et al. Chemical synthesis and cytotoxicity of some azinomycin analogues devoid of the 1-azabicyclo[3.1.0]hexane subunit. Bioorg Med Chem Lett. 2000 Feb 7;10(3):239-41.
丝裂霉素C（Mitomycin C）是一种从凯撒链霉菌或紫菜链霉菌中分离出来的抗生素，通过共价丝裂霉素C-DNA抑制PC3细胞中的DNA合成，EC50值为0.14μM。丝裂霉素C是一种抗生素，在临床前和临床研究中显示出抗肿瘤活性，广泛用于治疗各种癌症。研究结果表明，5-FU联合丝裂霉素C在结直肠癌的体外治疗中比单一疗法更有效。丝裂霉素C与其他细胞毒性药物如卡培他滨和雷立泰联合治疗结直肠癌的效果更好。丝裂霉素C不仅增强了TRAIL诱导的HCT116（p53-/-）结肠癌细胞凋亡，而且使结肠癌细胞HT-29对细胞因子敏感。丝裂霉素C下调细胞存活蛋白，包括Bcl2、Mcl-1和Bcl-XL，并上调促凋亡蛋白，包括Bax、Bim和TRAIL死亡受体DR4和DR5。此外，细胞实验结果表明，丝裂霉素C抑制HT-29细胞的IC50是40nM。丝裂霉素C在体内抗肿瘤中也发挥了重要作用。在体内实验中，丝裂霉素C显著抑制肿瘤生长，且不会影响TRAIL小鼠的体重，表明丝裂霉素C和TRAIL的治疗组合耐受性良好，在体内具有抗肿瘤活性。
| Cas No. | 50-07-7 | SDF | |
| 别名 | 丝裂霉素 C,Ametycine | ||
| 化学名 | ((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 | ||
| Canonical SMILES | NC(C1=O)=C(C)C(C2=C1[C@@H](COC(N)=O)[C@]3(OC)N2C[C@H]4[C@@H]3N4)=O | ||
| 分子式 | C15H18N4O5 | 分子量 | 334.33 |
| 溶解度 | ≥ 16.7mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9911 mL | 14.9553 mL | 29.9106 mL |
| 5 mM | 0.5982 mL | 2.9911 mL | 5.9821 mL |
| 10 mM | 0.2991 mL | 1.4955 mL | 2.9911 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。
Mitomycin C in the therapy of recurrent esophageal strictures: hype or hope?
Eur J Pediatr Surg.2013 Jan 1;31(1):88-94.PMID: 22517516DOI: 10.1055/s-0032-1311695.
Introduction: Esophageal strictures refractory to conservative treatment represent a major problem in children. The application of Mitomycin C to the site of stricture has been introduced, but the experience with this novel approach remains very limited. Methods: Systematic review of publications on the topical application of Mitomycin C in children with persistent esophageal stricture. Results: We identified 11 publications including 31 cases. The underlying cause of stricture was caustic ingestion in 19 (61.2%), esophageal surgery in 7 (22.6%), and others in 5 children (16.2%). The median age of the patients was 48 months (range 4 to 276 months). In the majority of cases cotton pledgets soaked in solution of Mitomycin C were applied endoscopically. Various other techniques such as drug-eluting stents were used. Mitomycin C was applied from 1 to 12 times within intervals from 1 to 12 weeks. The concentrations of Mitomycin C varied considerably between 0.1 and 1 mg/mL. After a mean follow-up time of 22 (6 to 60) months complete relief of symptoms was reported for 21 children (67.7%), and 6 (19.4%) had a partial relief. In four children (12.9%) Mitomycin C treatment failed. No direct or indirect adverse effects were reported. Conclusion: The short-term results of topical Mitomycin C application for refractory esophageal stricture reported in the literature are very encouraging. Prospective studies are mandatory to determine the optimal time points, dosage, and modalities of treatment before a recommendation can be given.
Mitomycin C in corneal refractive surgery
Surv Ophthalmol.2009 Jul-Aug;54(4):487-502.PMID: 19539836DOI: 10.1016/j.survophthal.2009.04.002.
Mitomycin C has played a deciding role in the current revival of excimer laser surface ablation techniques. We review the literature regarding mechanism of action of mitomycin C, histological effects on the cornea, and indications, dose, exposure time, and toxicity of mitomycin C in corneal refractive surgery. Mitomycin C is an alkylating agent with cytotoxic and antiproliferative effects that reduces the myofibroblast repopulation after laser surface ablation and, therefore, reduces the risk of postoperative corneal haze. It is used prophylactically to avoid haze after primary surface ablation and therapeutically to treat pre-existing haze. There is no definite evidence that establishes an exact diopter limit or ablation depth at which to apply prophylactic mitomycin C. It is usually applied at a concentration of 0.2mg/ml (0.02%) for 12 to 120 seconds over the ablated stroma, although some studies suggest that lower concentrations (0.01%, 0.002%) could also be effective in preventing haze when treating low to moderate myopia. This dose of mitomycin C has not been associated with any clinically relevant epithelial corneal toxicity. Its effect on the endothelium is more controversial: two studies report a decrease in endothelial cell density, but the majority of reports suggest that the endothelium is not altered. Regarding mitomycin C's effect on keratocyte population, although animal studies report keratocyte depletion after its use, longer follow-up suggested that the initial keratocyte depletion does not persist over time.
Mitomycin C and endoscopic sinus surgery: where are we?
Curr Opin Otolaryngol Head Neck Surg2007 Feb;15(1):40-3.PMID: 17211182DOI: 10.1097/MOO.0b013e328011bcae
Purpose of review: Mitomycin C has been used successfully in various ophthalmologic and, more recently, otolaryngologic procedures. Its modulation of fibroblast activity allows for decreased scarring and fibrosis. Several recent trials have examined the efficacy of mitomycin C in reducing synechia and stenosis following endoscopic sinus surgery. Recent findings: Basic science studies using fibroblast cell lines have demonstrated a dose-dependent suppression of activity with the use of mitomycin C. This is further supported by animal studies that have shown lower rates of maxillary ostial restenosis following application of mitomycin C. No human trial, however, has demonstrated a statistically significant impact of mitomycin C on the incidence of postoperative synechia or stenosis following sinus surgery. The limitations of the literature are discussed. Summary: The antiproliferative properties of mitomycin C may theoretically decrease the incidence of synechia and stenosis following endoscopic sinus surgery. Although this is supported by basic science studies and its successful use in other fields, the clinical evidence to date has not shown the application of mitomycin C to be effective in preventing stenosis after endoscopic sinus surgery. Future prospective studies are required before definitive conclusions can be made.
Topical versus interlesional mitomycin C in auricular keloids
Acta Otorrinolaringol Esp (Engl Ed)2021 Sep-Oct;72(5):280-287.PMID: 34535218DOI: 10.1016/j.otoeng.2020.06.006
Background: The Keloid is an elevated fibrous scar that may extend beyond the borders of the original wound. Object: To compare between topical and intralesional mitomycin C in the treatment of auricular keloids. Patients and methods: Prospective randomized study in which 40 patients with auricular keloids were included. The patients were divided into 2 groups, Group I included 32 patients who underwent topical mitomycin C application after the surgical removal of the auricular keloids, while Group II included 8 cases who underwent intra-lesional injection of mitomycin C after surgical removal of the auricular keloids. Results: The two groups showed no significant difference regarding patient or lesion criteria (p>.05). VSS decreased significantly from 10.63 and 11.0 down to 1.38 and 3.0 after treatment in the topical and intra-lesional groups respectively (p<.001). However, greater improvement and satisfaction was detected in the topical group. Conclusion: Both topical and intra-lesional mitomycin C injection are effective methods in managing auricular keloids. However, better VSS scores and patient satisfaction are reported with topical administration.
Intravesical mitomycin C for superficial transitional cell carcinoma
Expert Rev Anticancer Ther 2006 Aug;6(8):1273-82.PMID: 23296407DOI: 10.1586/14737140.6.8.1273.
Intravesical instillation of mitomycin C after a transurethral resection of a bladder tumor constitutes a standard treatment modality in the management of superficial transitional cell carcinoma in the urinary bladder. An immediate instillation of mitomycin C after transurethral resection has been shown to reduce the recurrence rate of superficial transitional cell carcinoma. Intravesical mitomycin C is generally considered to be a safe treatment option, but the past few years have seen the publication of a number of case reports on severe complications following mitomycin C instillation. This article reports on the mode of action, as well as the intravesical effects and current indications for mitomycin C instillation. This review will summarize the oncological benefits of mitomycin C in comparison with other intravesical treatments, such as bacillus Calmette-Guérin, and elucidate the incidence and types of possible complications associated with intravesical mitomycin C chemotherapy.