Inhibition of apoptosis-driven regression of hair bulb

Hair exerts a range of functions including thermoregulation, physical protection, sensory activity. Mature and actively growing hair follicles become anchored in the subcutis, and regenerate by spontaneous repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and quiescence (telogen). At the base of this cycle is the ability of hair follicle (HF) stem cells to briefly exit their quiescent status to generate transient amplifying progeny. It seems that, within a single hair follicle, periodic activation of beta-catenin in bulge stem cells is responsible for their cyclic activity. During HF growth and hair production, the activity of factors promoting the proliferation, differentiation and survival predominates. HF regression is characterized by activation of pathways that induce apoptosis in HF cells. Data Obtained from murine and human HF suggest that apoptosis could be controlled by extrinsic and intrinsic pathways. The most susceptible to apoptosis are the majority of the folliculare epithelial cells and melanocytes, whereas dermal papilla fibroblasts, some of the keratinocytes and melanocytes selected for survival, are resistant to apoptosis. We focused our study on investigating the effect of new therapeutic molecules capable of counteracting the regression phase. We have tested our working hypothesis on HFDPC cells, grown in culture in Follicle Dermal Papilla Growth Medium, and apoptosis was induced by 24 hours incubation with 1 μM staurosporin. This treatment resulted in a marked activation of Caspase-3 accompanied by cytoskeletal degradation, nuclear blebbing, and cellular fragmentation. The addition of spermidin or rutine in the micromolar range concentration reduced staurosporin-induced caspase activity by over 50%, when the two agents were added simultaneously equal levels of caspase-3 inhibition was achieved with concentration 10 fold lower. Zeaxantine alone was ineffective, however when added to the combined spermidin and rutine treatment, the staurosporin-induced caspase activity was almost totally counteracted and the enzymatic activity was significantly reduced. These combined treatment was also effective in preventing staurosporin-mediated cellular damage. The extent of cell loss was greatly reduced and there was a total preservation and normal distribution of actin-tubulin cytoskeleton with normal cellular shape. Interestingly, our combined treatment also counteracted caspase-3 over-expression induced by staurosporin. In conclusion, this sperimental molecules can counteract HFDPC cells apoptosis and may represent an effective preventing treatment for the catagen phase of the hair bulb life cycle