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Title 

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

Authors 

Jihoon KimYu Jin LeeD S ShinS H JeonKwang Hee SonDong Cho HanSeung Nam JungTae Kwang OhByoung-Mog Kwon

Publisher 

Elsevier

Issue Date 

2011

Citation 

Bioorganic & Medicinal Chemistry, vol. 19, no. 24, pp. 7582-7589

Keywords 

AntitumorApoptosisBreast cancerCosmomycinSignal transducer and activator of transcription 3 (STAT3)

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 G0-G1 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.

ISSN 

0968-0896

Link 

http://dx.doi.org/10.1016/j.bmc.2011.10.025

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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