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Cosmomycin C inhibits signal transducer and activator of transcription 3 (STAT3) pathways in MDA-MB-468 breast cancer cell.

Abstract：

:The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated therapeutic strategy. To discover novel inhibitors of STAT3 activity, we screened against microbial natural products using a dual-luciferase assay. Using the microbial metabolome library, we identified cosmomycin C (CosC), which was isolated from the mycelium extract of Streptomyces sp. KCTC19769, as a STAT3 pathway inhibitor. CosC inhibited STAT3 (Tyr705) phosphorylation and subsequent nuclear translocation in MDA-MB-468 breast cancer cells. CosC-mediated inhibition of STAT3 signaling pathway was confirmed by suppressed expression of STAT3 downstream target proteins including cyclin D1, Bcl-xL, survivin, Mcl-1, and VEGF in CosC-treated MDA-MB-468 cells. Flow cytometry showed that CosC caused accumulation in the G(0)-G(1) phase of the cell cycle and induced apoptosis via PARP cleavage and caspase-3 activation. Based on these findings, CosC may be a potential candidate for modulation of STAT3 pathway.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Kim J,Lee YJ,Shin DS,Jeon SH,Son KH,Han DC,Jung SN,Oh TK,Kwon BM

doi

10.1016/j.bmc.2011.10.025

subject

Has Abstract

pub_date

2011-12-15 00:00:00

pages

7582-9

issue

24

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00833-9

journal_volume

19

pub_type

杂志文章

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