RRC ID |
54761
|
Author |
Lin Y, Chen Y, Ukaji T, Okada S, Umezawa K.
|
Title |
Isolation of ketomycin from Actinomycetes as an inhibitor of 2D and 3D cancer cell invasion.
|
Journal |
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.
|
Volume |
72(3)
|
Pages |
148-154
|
Published |
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
|
Times Cited |
1
|
Resource |
Human and Animal Cells |
MCF7(RCB1904) |