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

Abstract:

:We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. In drug combination studies, we found that lysocellin treatment weakened the cytotoxic activity of etoposide in MG63 cells using a colony-formation assay. To study the in vivo efficacy of lysocellin, we isolated a novel compound related to lysocellin from the same streptomycete, and found that the novel drug is converted to lysocellin in vivo and decreases etoposide-induced alopecia in a neonatal rat model. We raise the possibility that this novel drug, named 'alopestatin', may be a promising agent against alopecia.

journal_name

Int J Oncol

authors

Takahara Y,Yogosawa S,Maruyama S,Watanabe N,Yokoyama H,Fukasawa K,Sukenaga Y,Kamiyama J,Izumi M,Wakada M,Zhang H,Yoshizawa K,Kawa S,Nikaido T,Sakai T

keywords:

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

823-9

issue

4

eissn

1019-6439

issn

1791-2423

journal_volume

28

pub_type

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