title: NF-κB Is a Potential Molecular Drug Target in Triple-Negative Breast Cancers.
abstract: Breast cancer continues to cause significant burden in global health morbidity and mortality. Triple-negative breast cancers (TNBCs) are highly aggressive with poor prognosis and are characterized by lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (Her-2). TNBCs are often resistant to cytotoxic chemotherapy and pose major difficulty in achieving personalized medicine due to their molecular heterogeneity. There is increasing evidence that the aberrant activation of nuclear factor (NF)-κB signaling is a frequent characteristic of TNBCs. We evaluated the effects of different potential NF-κB inhibitors, such as bisindolylmaleimide I (BIS, a selective protein kinase C [PKC] inhibitor), MG132 (a proteasome inhibitor), curcumin (endowed with pleiotropic activities), and dehydroxymethylepoxyquinomicin (an inhibitor of NF-κB translocation into the nucleus) on the constitutive activation of NF-κB present in three TNBC cell lines (SUM 149, SUM 159, and MDA-MB-231). We also evaluated whether MDA-9/Syntenin plays a role in NF-κB activation, as observed in other cancer types. Indeed, silencing experiments with a siRNA anti-MDA-9/Syntenin produced a very strong reduction of NF-κB activation in all the three TNBC cell lines. We conclude that different approaches targeting NF-κB activation might potentially prove useful for innovation in anticancer drug development for TNBCs. Further research that bridge preclinical and clinical investigations with NF-κB inhibitors would be timely and warranted.
authors.affiliation: Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro," School of Medicine, University of Palermo , Palermo, Italy .
authors.forename: Paola
authors.initials: P
authors.lastname: Poma
authors.affiliation: Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro," School of Medicine, University of Palermo , Palermo, Italy .
authors.forename: Manuela
authors.initials: M
authors.lastname: Labbozzetta
authors.affiliation: Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro," School of Medicine, University of Palermo , Palermo, Italy .
authors.forename: Natale
authors.initials: N
authors.lastname: D'Alessandro
authors.affiliation: Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro," School of Medicine, University of Palermo , Palermo, Italy .
authors.forename: Monica
authors.initials: M
authors.lastname: Notarbartolo
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D057285:Precision Medicine; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*
chemical_list: D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; C464444:dehydroxymethylepoxyquinomicin; D003474:Curcumin
keywords: NF-κB signaling; diagnostics; drug targets; personalized medicine; triple-negative breast cancer