Antibiotic Tetrocarcin-A Down-regulates JAM-A, IAPs and Induces Apoptosis in Triple-negative Breast Cancer Models.
Anticancer Res
; 39(3): 1197-1204, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-30842150
ABSTRACT
BACKGROUND/AIM:
Triple-negative breast cancers (TNBC) lack expression of three important receptors, and have limited treatment options. High expression of junctional adhesion molecule-A (JAM-A) has been linked with aggressive tumor phenotypes including TNBC. This study aimed to evaluate the bioactivity of a JAM-A-down-regulating compound, Tetrocarcin-A, in TNBC. MATERIALS ANDMETHODS:
TNBC cell viability, colony formation and xenograft growth were examined in Tetrocarcin-A-treated HCC38 human cells, 4T1 mouse cells or patient-derived primary cells. Protein expression of cell fate signaling effectors was examined by immunoblotting (versus transient JAM-A gene silencing). Apoptotic pathways were investigated in parallel.RESULTS:
Tetrocarcin-A reduced TNBC cell viability in vitro and in an in ovo/semi-in vivo xenograft model. Tetrocarcin-A-induced JAM-A down-regulation and reduced ERK phosphorylation, followed by c-FOS phosphorylation on its transcription-regulating residue, which down-regulated several inhibitor of apoptosis (IAP) proteins and induced caspase-dependent intrinsic pathway of apoptosis.CONCLUSION:
Tetrocarcin-A merits further investigation as a novel anti-tumor agent in TNBC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Inhibidoras de la Apoptosis
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Neoplasias de la Mama Triple Negativas
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Aminoglicósidos
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Irlanda