Lysocellin, a metabolite of the novel drug ‘alopestatin’, induces G1 arrest and prevents cytotoxicity induced by etoposide

Lysocellin, a polyether antibiotic from a streptomycete, was found to induce G1 phase arrest in human osteosarcoma MG63 cells by up-regulating p21WAF1/Cip1 and down-regulating cyclin D1 at the mRNA level, with cyclin D1 also being down-regulated via a proteasome-dependent pathway. In combination with etoposide, lysocellin reduced the drug's cytotoxicity in MG63 cells. A related novel compound, alopestatin, was isolated and shown to convert to lysocellin in vivo, reducing etoposide-induced alopecia in a neonatal rat model, suggesting its potential as a promising agent against alopecia.