Mitomycin C
(Synonyms: 丝裂霉素 C,Ametycine) 目录号 : GC12353
Mitomycin C是一种抗生素,从链霉菌(Streptomyces Caespitosus)或淡紫色链霉菌(Streptomyces Lavendulae)中分离出来。
Cas No.:50-07-7
Sample solution is provided at 25 µL, 10mM.
Mitomycin C is an antibiotic isolated from Streptomyces Caespitosus or Streptomyces Lavendulae. Mitomycin C inhibits DNA synthesis by forming covalent mitomycin C-DNA adducts with DNA, with an EC50 value of 0.14 μM in PC3 cells.
Mitomycin C can enhance the apoptosis effect induced by TRAIL on HCT116 (p53-/-) colon cancer cells, and can also make TRAIL-resistant colon cancer cells HT-29 sensitive to this cytokine. The IC50 of Mitomycin C on HT-29 cells is 40nM[1,2]. At the mechanistic level, Mitomycin C down-regulates cell survival-related proteins including Bcl2, Mcl-1, and Bcl-XL, and up-regulates the expression of pro-apoptotic proteins such as Bax, Bim, and TRAIL death receptors DR4 and DR5[1,2].
Mitomycin C has shown anti-tumor effects in animal experiments. In in vivo experiments, Mitomycin C significantly inhibited tumor growth and did not affect the body weight of mice under TRAIL treatment, indicating that the therapeutic combination of Mitomycin C and TRAIL was well tolerated in vivo and had antitumor activity[1].
Mitomycin C has demonstrated anti-tumor activity in preclinical and clinical studies and is widely used to treat various cancers. Mitomycin C is known to have synergistic effects with Capecitabine and Irinotecan. Studies have shown that in colorectal cancer, combination therapy of 5-FU or Raltiterxed with Mitomycin C is more effective than single agents[1].
In cell culture experiments, the recommended concentration of Mitomycin C is 0.2-20μg/mL.
Mitomycin C是一种抗生素,从链霉菌(Streptomyces Caespitosus)或淡紫色链霉菌(Streptomyces Lavendulae)中分离出来。Mitomycin C通过与DNA形成共价mitomycin C-DNA加合物来抑制DNA合成,在PC3细胞中的EC50值为0.14μM。
Mitomycin C可以增强TRAIL对HCT116(p53-/-)结肠癌细胞诱导的凋亡作用,也能够使TRAIL耐药性结肠癌细胞HT-29对这种细胞因子变得敏感。Mitomycin C在HT-29细胞上的IC50为40nM[1,2]。在机制水平上,Mitomycin C下调了包括Bcl2、Mcl-1和Bcl-XL在内的细胞存活相关蛋白,并上调了促凋亡蛋白如Bax、Bim以及TRAIL死亡受体DR4和DR5的表达[1,2]。
Mitomycin C在动物实验中显示出抗肿瘤效果。在体内实验中,Mitomycin C显著抑制了肿瘤的生长,并且不影响TRAIL治疗下小鼠的体重,这表明Mitomycin C和TRAIL的治疗组合在体内耐受性良好并具有抗肿瘤活性[1]。
Mitomycin C已在临床前和临床研究中表现出抗肿瘤活性,并广泛用于治疗各种癌症。已知Mitomycin C与卡培他滨(Capecitabine)和伊立替康(Irinotecan)具有协同作用。研究表明,在结直肠癌中,5-FU或雷替曲塞(Raltiterxed)与Mitomycin C的联合治疗比单药更有效[1]。
在细胞培养实验中,Mitomycin C的建议浓度为0.2-20μg/mL。
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.
Cell experiment [1, 2]: | |
Cell lines |
HCT116, HT-29 |
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. |
Reaction Conditions |
5 μM,12 or 24h |
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]: | |
Animal models |
Nude mice (6 weeks) injected subcutaneously with 1 × 106 HCT116 (p53−/−) or 2 × 106 HT-29 cells mixed with Matrigel |
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. |
Dosage form |
1 mg/kg, Intraperitoneal injection |
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. |
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. |
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 |
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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 |
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