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  3. Mechanism of action

About Mitomycin-C Kyowa

Mechanism of action

Site of action

Inside of tumour cells.

Mechanism of action

The activation of Mitomycin-C begins with the reduction of the quinone structure. One-electron reduction is mediated by cytochrome P-450 reductase, xanthine oxidase, cytochrome b5 reductase, etc., and two-electron reduction is mediated by DT-diaphorase, xanthine dehydrogenase, etc.1-3). Mitomycin-C is metabolized to a number of active forms by enzymatic reduction (Figure 1), which are thought to exert antineoplastic activity through the formation of cross linkage to DNA (Figures 2-4 and 2-5: interstrand cross-link and intrastrand cross-link), alkylation (Figures 2-1 to 2-3)1-4), and DNA strand breakage with free radicals5).

Metabolic pathway for activation Mitomycin-C/DNA binding forms

Cell-killing activity of Mitomycin-C in different phases of the cell cycle

The sensitivity of HeLa cells in different phases of the cell cycle to Mitomycin-C was determined. Cells in the latter half of the pre-DNA synthesis (G1) phase through the former half of the DNA synthesis (S) phase were shown to be highly sensitive to Mitomycin-C.

Viability of HeLa cells after exposure to Mitomycin-C in different phases of the cell cycle

References

1. Cummings J et al. Eur J Cancer 1995; 31A: 1928-33
2. Cummings J et al. Biochem Pharmacol 1998; 56: 405-14
3. Tomasz M et al. Pharmacol Ther 1997; 76: 73-87
4. Szybalski W et al. Fed Proc 1964; 23: 946-57
5. Tomasz M et al. Chem Biol Interact 1976; 13: 89-97

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