Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression

SPECIFIC AIMSThe synthetic nontoxic Tellurium compound AS101, currently used in clinical trials on cancer patients, has been found to protect cancer patients from chemotherapy-induced bone marrow toxicity and alopecia. The aim of the present study was to evaluate the ability of AS101 to induce hair growth and to gain insight into the mechanism of action of this effect.PRINCIPAL FINDINGS1. Induction of hair growth by AS101 in miceThe ability of AS101 to induce hair growth was studied in several mouse models. In nude mice AS101 induced a pronounced dose-dependent increase in hair growth when administered either systematically (i.p.), orally, or topically (Fig. 1⤻ ). It appears that exogenously administered AS101 stimulates hair growth in nu/nu athymic mice by stimulating follicular proliferation (increase in BrdU-labeled follicular keratinocytes) and inducing normalization of the nu/nu follicular keratin differentiation defect (relatively normal follicles containing well-differentiated straight hair shafts ...