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.
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.
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。