Mitomycin C

[Description]:

Mitomycin C is an antitumor drug and antibiotic that shows extraordinary ability to inhibit DNA synthesis.

[Related Catalog]:

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Research Areas >> Cancer

Natural Products >> Others

[Target]

DNA synthesis[1]

[In Vitro]

The HCT116 (p53-/-) cells are minimally sensitive to either Mitomycin C or TRAIL alone. However, surprisingly, combination treatment with MMC and TRAIL decreases cell viability significantly. Although Mitomycin C and TRAIL alone are moderately effective, Mitomycin C substantially enhances the effect of TRAIL on suppression of the cell proliferation. Mitomycin C and TRAIL treatment alone induces 9.5% and 35.0% apoptosis, respectively. However, combination treatment with Mitomycin C and TRAIL enhances apoptosis to 66.6%[1]. Mitomycin C is a cytotoxic chemotherapeutic agent that causes DNA damage in the form of DNA cross-links as well as a variety of DNA monoadducts and is known to induce p53[2].

[In Vivo]

Mice bearing xenografted HCT116 (p53-/-) colon tumors and HT-29 colon tumors are treated with Mitomycin C (i.p., 1 mg/kg) and TRAIL (i.v., 100 μg) every other day. Animals are treated with 10 consecutive cycles of the combination therapy regimen. The combination therapy suppresses tumor growth significantly and does not impact the weight of the mice, indicating that the therapeutic combination of Mitomycin C and TRAIL is well-tolerated and has anti-tumor activity in vivo[1]. Intravesical Mitomycin C instillations has an effect on body weight that is not observed in normal, NaCl instilled or Epirubicin instilled rats. After 3 consecutive weekly instillations of 1 mg/mL Mitomycin C there is almost no weight gain, whereas rats in the other 3 groups has a statistically significant weight gain compared with MMC treated rats[3].

[Cell Assay]

Colon adenocarcinoma HCT116 and HT-29 human colon cancer cells are used. The CellTiter-Glo Luminescent Cell Viability Assay is used to measure cell viability, which use a unique, stable form of luciferase to measure ATP as an indicator of viable cells, and the luminescent signal produced is proportional to the number of viable cells present in culture. Cells are pretreated with Mitomycin C (5 μM) for 12 h or 24 h, and then exposed to different concentrations of TRAIL for 12 h. An equal volume (100 μL) of CellTiter-GloTM reagent is added and the solution is mixed gently for 2 min on an orbital shaker. Mixture is incubated at room temperature for 10 min to allow luminescent signal to stabilize, and then imaging is performed using the Xenogen IVIS system to quantify the cell viability[1].

[Animal admin]

Mice[1] Four- to 6-wk-old NCr nude mice are treated with Mitomycin C (1 mg/kg) by intraperitoneal injection for 24 h, followed by one intravenous dose of purified rhTRAIL (100 μg). As a negative control, a subset of the mice are injected (i.p. and i.v.) with saline (vehicle) at the same frequency of treatment. Animals are treated for 3 consecutive weeks. The tumor size is monitored every week using caliper measurements of the tumor volume. Rats[3] Young adult female Wistar rats at age 13 weeks with a median weight of 217 g (range 187 to 255) are randomized into 4 groups of 10 each, namely a normal group with no instillations, an NaCl 0.9% or placebo group that received instillations with the solvent of the chemotherapeutic agents, an Mitomycin C (1 mg/mL) group and an Epirubicin (1 mg/mL) group.

[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]. Abbas T, et al. Differential activation of p53 by the various adducts of mitomycin C. J Biol Chem. 2002 Oct 25;277(43):40513-9.

[3]. Michielsen D, et al. Mitomycin C and epirubicin: functional bladder damage in rats after repeat intravesical instillations. J Urol. 2005 Jun;173(6):2166-70.

[Related Small Molecules]

[ Density]:
1.9±0.1 g/cm3

[ Boiling Point ]:
532.0±60.0 °C at 760 mmHg

[ Melting Point ]:
360 °C

[ Molecular Formula ]:
C₁₅H₁₈N₄O₅

[ Molecular Weight ]:
334.327

[ Flash Point ]:
275.5±32.9 °C

[ Exact Mass ]:
334.127716

[ PSA ]:
146.89000

[ LogP ]:
-0.27

[ Vapour Pressure ]:
0.0±3.2 mmHg at 25°C

[ Index of Refraction ]:
1.828

[ Stability ]:
Stable. Incompatible with strong acids, strong bases, strong oxidizing agents.

[ Water Solubility ]:
soluble

Click to get detail MSDS

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300-H351

[ Precautionary Statements ]:
P201-P202-P280-P301 + P310 + P330-P308 + P313-P501

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T:Toxic

[ Risk Phrases ]:
R25;R40

[ Safety Phrases ]:
S36/37-S45-S28A-S28

[ RIDADR ]:
UN 3462 6.1/PG 2

[ WGK Germany ]:
3

[ RTECS ]:
CN0700000

[ Packaging Group ]:
II

[ Hazard Class ]:
6.1(a)

Click to get detail synthetic route

Precursor

DownStream

DNA damage-specific deubiquitination regulates Rad18 functions to suppress mutagenesis.

J. Cell Biol. 206(2) , 183-97, (2014)

Deoxyribonucleic acid (DNA) lesions encountered during replication are often bypassed using DNA damage tolerance (DDT) pathways to avoid prolonged fork stalling and allow for completion of DNA replica...

Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes.

J. Toxicol. Environ. Health A 77(21) , 1269-80, (2014)

Fluoride generated the attention of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and with in vivo experimental models. Interest in ...

Piperine inhibits the growth and motility of triple-negative breast cancer cells.

Cancer Lett. 357(1) , 129-40, (2014)

Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (T...

Names

Biological Activity

Chemical & Physical Properties

MSDS

Click to get detail MSDS

Safety Information

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Related Compounds