Mitomycin C (Synonyms: Ametycine)

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.