Inhibition of Metastatic Squamous Cell Carcinoma Development in Protein Kinase C Epsilon Transgenic Mice by Alpha-Difluoromethylornithine with Hair Follicle Degeneration and Hair Loss

June 2003 in “ PubMed ”

Deric L. Wheeler, Kristin J. Ness, Terry D. Oberley, Ajit Kumar Verma

alpha-difluoromethylornithine ornithine decarboxylase protein kinase C epsilon TPA polyamine biosynthesis putrescine hair follicle degeneration hair loss DFMO ODC PKC epsilon

TLDR Alpha-difluoromethylornithine prevents cancer in mice but causes hair loss.

The study investigated the effects of TPA-stimulated polyamine biosynthesis on metastatic squamous cell carcinoma (mSCC) development in protein kinase C epsilon (PKC epsilon) transgenic mice. It was found that TPA treatment significantly increased epidermal ornithine decarboxylase (ODC) activity and putrescine levels in these mice compared to wild-type littermates. The development of mSCC was completely prevented by administering alpha-difluoromethylornithine (DFMO), an ODC inhibitor, in the drinking water during TPA promotion. However, this treatment resulted in marked hair loss and a decrease in intact hair follicles in the transgenic mice. The findings suggested a link between TPA-induced ODC activity, putrescine accumulation, hair follicle maintenance, and mSCC development, with the observed hair loss being a novel side effect not previously reported in other cancer prevention models.

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Inhibition of Metastatic Squamous Cell Carcinoma Development in Protein Kinase C Epsilon Transgenic Mice by Alpha-Difluoromethylornithine with Hair Follicle Degeneration and Hair Loss

Research cited in this study

research Involvement of Follicular Stem Cells in Forming Not Only the Follicle but Also the Epidermis

research Transgenic Mice Overexpressing Protein Kinase C Epsilon in Their Epidermis Exhibit Reduced Papilloma Burden but Enhanced Carcinoma Formation After Tumor Promotion

research Overexpression of Protein Kinase C-α in the Epidermis of Transgenic Mice Results in Striking Alterations in Phorbol Ester-Induced Inflammation and COX-2, MIP-2, and TNF-α Expression but Not Tumor Promotion

research Dynamic Expression of Ornithine Decarboxylase in Hair Growth

research Modulation of Murine Hair Follicle Function by Alterations in Ornithine Decarboxylase Activity

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