Mitomycin C

By Bushra Fatima, Dec. 2016

What is it?

Mitomycin C is a member of the mitomycin family of compounds, characterized by the presence of an aziridine ring. Mitomycin C was initially discovered as an antibiotic, but due to its antineoplastic properties has since been used in various cancer treatments. It is known to form covalent bonds with the DNA double helix, and these crosslinkages are the mechanism through which it causes cell death [1].

When was it discovered?

In late 1950s Dr Toju Hata and Dr. Shigetoshi Wakagi isolated mitomycin C from the fermentation broth of Streptomyces caespitosus [2].

Who produces it?

Mitomycin C is naturally produced by two Streptomyces species –Streptomyces caespitosus and Streptomyces lavendula, found in soil [3].

Where is it found?

It is present in the fermentation broth of Streptomyces species.

Why is it important?

Mitomycin C is a cytotoxic compound which, upon reduction, crosslinks the DNA double strands. This leads to inhibition of DNA synthesis, which in turn prevents cell proliferation. These antitumor properties of mitomycin C have led to its frequent use in treatment of various ocular tumors [4], along with other types of cancers. Mitomycin C is also used as an antibiotic agent due to its proficiency in killing bacteria through DNA crosslinkages [1].

Why was it chosen?

Mitomycin C has been shown to induce Streptococcus mitis prophage, SM1 [5].

Structure:

m1

Fig 1. Mitomycin C structure from Wikipedia

m2

Fig. 2. Mechanism of DNA cross-linking from Tomasz, Maria. “Mitomycin C: Small, Fast and Deadly (but Very Selective).” Chemistry & Biology 2.9 (1995): 575-79.

 

References

[1] Tomasz, Maria. “Mitomycin C: Small, Fast and Deadly (but Very Selective).” Chemistry & Biology 2.9 (1995): 575-79. Web.

[2] Nemade, Hemant, Hussein Tukmatchy, and Peter Thompson. “Fri-10 Mitomycin-C: Historical Aspects Of The Discovery Of Most Commonly Used Chemotherapy Agent In Urology.” The Journal of Urology 193.4 (2015): n. pag. Web

[3] Danshiitsoodol, Narandalai, Catherine Azzariti De Pinho, Yasuyuki Matoba, Takanori Kumagai, and Masanori Sugiyama. “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.” Journal of Molecular Biology 360.2 (2006): 398-408. Web.

[4] Mearza, Ali A., and Ioannis M. Aslanides. “Uses and Complications of Mitomycin C in Ophthalmology.” Expert Opinion on Drug Safety 6.1 (2006): 27-32. Web.

[5] Willner, Dana et al. “Metagenomic Detection of Phage-Encoded Platelet-Binding Factors in the Human Oral Cavity.” Proceedings of the National Academy of Sciences of the United States of America 108.Suppl 1 (2011): 4547–4553. PMC. Web. 30 Nov. 2016.