NF-kB Is a Potential Molecular Drug Target in Triple-Negative Breast Cancers

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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)-kB signaling is a frequent characteristic of TNBCs. We evaluated the effects of different potential NF-kB 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-kB translocation into the nucleus) on the constitutive activation of NF-kB present in three TNBC cell lines (SUM149, SUM159, and MDA-MB-231). Wealso evaluated whether MDA-9/Syntenin plays a role in NF-kB activation, as observed in other cancer types. Indeed, silencing experiments with a siRNA anti-MDA-9/Syntenin produced a very strong reduction of NF-kB activation in all the three TNBC cell lines. We conclude that different approaches targeting NF-kB activation might potentially prove useful for innovation in anticancer drug development for TNBCs. Further research that bridge preclinical and clinical investigations with NF-kB inhibitors would be timely and warranted.
Lingua originaleEnglish
pagine (da-a)225-231
Numero di pagine7
RivistaOMICS
Volume21
Stato di pubblicazionePublished - 2017

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Triple Negative Breast Neoplasms
Syntenins
Pharmaceutical Preparations
Cell Line
Precision Medicine
Proteasome Inhibitors
Curcumin
Protein C Inhibitor
Progesterone Receptors
Protein Kinase Inhibitors
Estrogen Receptors
Protein Kinase C
Small Interfering RNA
Breast Neoplasms
Morbidity
Drug Therapy
Mortality
Research

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Biochemistry

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title = "NF-kB 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)-kB signaling is a frequent characteristic of TNBCs. We evaluated the effects of different potential NF-kB 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-kB translocation into the nucleus) on the constitutive activation of NF-kB present in three TNBC cell lines (SUM149, SUM159, and MDA-MB-231). Wealso evaluated whether MDA-9/Syntenin plays a role in NF-kB activation, as observed in other cancer types. Indeed, silencing experiments with a siRNA anti-MDA-9/Syntenin produced a very strong reduction of NF-kB activation in all the three TNBC cell lines. We conclude that different approaches targeting NF-kB activation might potentially prove useful for innovation in anticancer drug development for TNBCs. Further research that bridge preclinical and clinical investigations with NF-kB inhibitors would be timely and warranted.",
author = "Natale D'Alessandro and Manuela Labbozzetta and {Notarbartolo Di Villarosa}, Monica and Paola Poma",
year = "2017",
language = "English",
volume = "21",
pages = "225--231",
journal = "OMICS A Journal of Integrative Biology",
issn = "1536-2310",
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TY - JOUR

T1 - NF-kB Is a Potential Molecular Drug Target in Triple-Negative Breast Cancers

AU - D'Alessandro, Natale

AU - Labbozzetta, Manuela

AU - Notarbartolo Di Villarosa, Monica

AU - Poma, Paola

PY - 2017

Y1 - 2017

N2 - 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)-kB signaling is a frequent characteristic of TNBCs. We evaluated the effects of different potential NF-kB 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-kB translocation into the nucleus) on the constitutive activation of NF-kB present in three TNBC cell lines (SUM149, SUM159, and MDA-MB-231). Wealso evaluated whether MDA-9/Syntenin plays a role in NF-kB activation, as observed in other cancer types. Indeed, silencing experiments with a siRNA anti-MDA-9/Syntenin produced a very strong reduction of NF-kB activation in all the three TNBC cell lines. We conclude that different approaches targeting NF-kB activation might potentially prove useful for innovation in anticancer drug development for TNBCs. Further research that bridge preclinical and clinical investigations with NF-kB inhibitors would be timely and warranted.

AB - 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)-kB signaling is a frequent characteristic of TNBCs. We evaluated the effects of different potential NF-kB 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-kB translocation into the nucleus) on the constitutive activation of NF-kB present in three TNBC cell lines (SUM149, SUM159, and MDA-MB-231). Wealso evaluated whether MDA-9/Syntenin plays a role in NF-kB activation, as observed in other cancer types. Indeed, silencing experiments with a siRNA anti-MDA-9/Syntenin produced a very strong reduction of NF-kB activation in all the three TNBC cell lines. We conclude that different approaches targeting NF-kB activation might potentially prove useful for innovation in anticancer drug development for TNBCs. Further research that bridge preclinical and clinical investigations with NF-kB inhibitors would be timely and warranted.

UR - http://hdl.handle.net/10447/225559

M3 - Article

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EP - 231

JO - OMICS A Journal of Integrative Biology

JF - OMICS A Journal of Integrative Biology

SN - 1536-2310

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