Description
Difluoromethylornithine (DFMO) exhibits anti-parasitic, anti-angiogenic, anti-metastatic, anticancer chemotherapeutic, and chemopreventive activities. DFMO inhibits ornithine decarboxylase, suppressing polyamine and thymidine synthesis. DFMO inhibits growth of Leishmania and Trypanosoma and is clinically used to treat African sleeping sickness. This compound suppresses breast cancer cell invasion by increasing PKA signaling and inhibits neovascularization in animal models. In other animal models, DFMO decreases the epithelial-to-mesenchymal transition (EMT), suppressing squamous cell carcinoma tumor growth; it also limits the development of esophageal tumors in vivo.
References
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Arumugam A, Weng Z, Talwelkar SS, et al. Inhibiting cycloxygenase and ornithine decarboxylase by diclofenac and alpha-difluoromethylornithine blocks cutaneous SCCs by targeting Akt-ERK axis. PLoS One. 2013 Nov 8;8(11):e80076. PMID: 24260338.
Xu H, Washington S, Verderame MF, et al. Activation of protein kinase A (PKA) signaling mitigates the antiproliferative and antiinvasive effects of alpha-difluoromethylornithine in breast cancer cells. Breast Cancer Res Treat. 2008 Jan;107(1):63-70. PMID: 17333334.
Lima e Silva R, Saishin Y, Saishin Y, et al. Suppression and regression of choroidal neovascularization by polyamine analogues. Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3323-30. PMID: 16123436.
Fong LY, Nguyen VT, Pegg AE, et al. Alpha-difluoromethylornithine induction of apoptosis: a mechanism which reverses pre-established cell proliferation and cancer initiation in esophageal carcinogenesis in zinc-deficient rats. Cancer Epidemiol Biomarkers Prev. 2001 Mar;10(3):191-9. PMID: 11303587.
