RRC ID 54761
著者 Lin Y, Chen Y, Ukaji T, Okada S, Umezawa K.
タイトル Isolation of ketomycin from Actinomycetes as an inhibitor of 2D and 3D cancer cell invasion.
ジャーナル J Antibiot (Tokyo)
Abstract Inhibitors of cancer cell migration and invasion should be useful to inhibit metastasis. Then, we have screened microbial culture filtrates for the inhibitors of cancer cell migration. As a result, we isolated an antibiotic ketomycin from a culture filtrate of Actinomycetes SF2912 as an inhibitor of cancer cell migration. It is a known antibiotic, but its biological activity on mammalian cells has not been reported. Ketomycin inhibited cellular migration and invasion in human breast carcinoma MDA-MB-231 and MCF-7 cells at the non-toxic concentrations. Ketomycin decreased the expressions of MMP-9 and MMP-11 in MDA-MB-231 cells. Knockdown of each gene by siRNA inhibited the cellular migration and invasion. Ketomycin was then found to inhibit the cellular NF-κB activity that may be involved in the upstream signaling. For the mechanism of NF-κB inhibition, ketomycin inhibited autophosphorylation of IKK-α/IKK-β. Ketomycin also inhibited the 3D-invasion of MDA-MB-231 cells at the non-toxic concentrations. Thus, ketomycin having a comparatively simple structure may become a seed of anti-metastasis agent.
巻・号 72(3)
ページ 148-154
公開日 2019-3-1
DOI 10.1038/s41429-018-0129-9
PII 10.1038/s41429-018-0129-9
PMID 30510246
MeSH Actinobacteria / growth & development Actinobacteria / metabolism* Antibiotics, Antineoplastic / isolation & purification* Antibiotics, Antineoplastic / pharmacology* Cell Line, Tumor Cell Movement / drug effects* Culture Media / chemistry Glyoxylates / isolation & purification Glyoxylates / pharmacology Humans Matrix Metalloproteinases / analysis NF-kappa B / antagonists & inhibitors
IF 2.446
引用数 1
リソース情報
ヒト・動物細胞 MCF7(RCB1904)