DL-α-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase.
Ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine, which is the committed step in polyamine synthesis.
DFMO inhibited the polyamine synthesis process and displayed antiangiogenic and cytostatic effects in many human tumor cells. In rat bladder carcinoma cell line-804G cells, DFMO inhibited the growth of 804G cells stimulated by Fraction I or by 10% FCS [2].
In female SENCAR mice with skin tumorigenesis model, both oral intake of DFMO (1.5-2.0% wt/vol) and intraperitoneal injection of DFMO (20mg,i.p. and 5mg,i.p.) reduced the sizes and numbers of skin tumor compared to control group [3].
References:
1. H. M. Wallace, A. V. Fraser and A. Hughes. A perspective of polyamine metabolism. Biochemistry Journal 376(Pt 1), 1-14 (2003).
2. Homma Y, Ozono S, Numata I, Seidenfeld J,et al. Alpha-Difluoromethylornithine inhibits cell growth stimulated by a tumor-promoting rat urinary fraction. Carcinogenesis. 1985 Jan;6(1):159-61.
3. Weeks CE, Herrmann AL, Nelson FR, Slaga TJ. Alpha-Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits tumor promoter-induced polyamine accumulation and carcinogenesis in mouse skin. Proc Natl Acad Sci U S A. 1982 Oct; 79(19):6028-32.