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

Studysummary In this study, severe hair loss occurred in PKC epsilon transgenic mice treated with DFMO during skin tumor prevention, highlighting a link between polyamine biosynthesis, hair follicle maintenance, and metastasis suppression. Our plain-language summary of this paper — not a Tressless recommendation.

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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