Cell lines

HCT116, HT-29

Preparation Method

Ten millimolar Mitomycin C is prepared in 100% dimethyl sulfoxide, stored as small aliquots at -80℃ 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 IC₅₀of 40 nM.

Animal models

Nude mice (6 weeks) injected subcutaneously with 1 × 106 HCT116 (p53–/–) or 2 × 10⁶HT-29 cells mixed with Matrigel

Preparation Method

Ten millimolar Mitomycin C is prepared in 100% dimethyl sulfoxide, stored as small aliquots at -80℃ 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.

• Cell Death Dis 12.4 (2021): 1-15.
• STAR protocols 2.3 (2021): 100789.
• Front Cardiovasc Med 9 (2022).
• Cells 11.19 (2022): 2951.

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 IC₅₀of 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.