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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. Therefore, it was served as a chemotherapeutic agent that has demonstrated its antitumor activity and has been used widely in treatment of various cancers. [1]Mitomycin-C enhanced TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis in p53 deficient colon cancer HCT116 cells. In the cell viability assay, pretreated with 5M with mitomycin C for 24h and then exposure to 25ng/ml TRAIL and 5M mitomycin C for 12h in HCT116 cells showed surprisingly decreased cell viability. In the crystal violet staining assay showed 5M mitomycin C combinated 25ng/ml TRAIL can substantially enhanced suppression effects of HCT116 cells. Pretreatment with 5M mitomycin C can enhanced TRAIL initiated processing of caspase-8, -9, -3 and cleavage of RARP (poly-ADP-ribose polymerase, substrate of caspase-3). The western blot assay showed in both HCT116 and HT29 cells, mitomycin C suppressed the expression anti apoptotic proteins Mcl-1, Bcl-2, Bcl-XL, and downregulated caspase-inhibitor c-IAP-1, XIAP, while upregulated expression of pro-apoptotic proteins Bax and Bim .[2]The NMRI-Fox1nu nude mice was inoculated subcutaneously and then randomized to several groups: treated with electrochemotherapy and administrated 5mM mitomycin C or electrochemotherapy only or 5mM mitomycin C only. Results showed that tumor volume reduced in electrochemotherapy plus mitomycin C group, and mice survival rates were greater in electrochemotherapy plus mitomycin C group and mitomycin C group only, compared controls(p＜0.001). The tumor response rate was 53% for mitomycin C alone.[3]References：[1] Danshiitsoodol N, de Pinho CA, Matoba Y, Kumagai T, Sugiyama M. The mitomycin C (MMC)-binding protein from MMC-producing microorganisms protects from the lethal effect of bleomycin: crystallographic analysis to elucidate the binding mode of the antibiotic to the protein. J Mol Biol (2006) 360 (2): 398–408[2] Hairong Cheng, Bo Hong, Lanlan Zhou, Joshua E. Allen, Guihua Tai, Robin Humphreys,David T. Dicker, Yingqiu Y. Liu & Wafik S. El-Deiry. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors. Cell Cycle (2012) 11(17):3312-3323[3] Juan Luis Vásquez, Per Ibsen, Henriette Lindberg, Julie Gehl. In Vitro and In Vivo Experiments on Electrochemotherapy for Bladder Cancer. Journal of Urology (2014)
Cell lines
Colon adenocarcinoma HCT116, HCT116 (p53-/-) colon cancer, HT-29 human colon cancer cells, human bladder cancer cell line SW780
Preparation method
The solubility of this compound in DMSO is >16.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition
1 μM, 5 μM, 10 μM, 12 h or 24 h
Applications
MMC substantially enhanced the effect of TRAIL on suppression of the HCT116 (p53-/-) cell proliferation. MMC enhanced TRAIL-induced apoptosis in TRAIL-resistant HT-29 cells. Pretreatment with MMC enhanced the sensitivity to lexatumumab and mapatumumab in HCT116 (p53-/-) cells and HT-29 cells. MMC sensitized colon cancer cells to TRAIL-induced apoptosis through downregulation of anti-apoptotic proteins, and upregulation of cell survival proteins and TRAIL death receptors.
Animal models
Mice bearing xenografted HCT116 (p53-/-) colon tumors and HT-29 colon tumors
Dosage form
Intraperitoneal injection, 1 mg/kg,
Application
Animals were treated with MMC (1 mg/kg) and intravenous dose of TRAIL (100 μg) every other day in combination therapy regimen for 10 consecutive cycles. The combination therapy significantly suppressed tumor growth with no effects on the weight.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1]. Hairong Cheng, Bo Hong, Lanlan Zhou, Joshua E. Allen, Guihua Tai, Robin Humphreys,David T. Dicker, Yingqiu Y. Liu & Wafik S. El-Deiry. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors. Cell Cycle (2012) 11(17):3312-3323
