ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
BCL2 and CASP8 regulation by NF-kappaB differentially affect mitochondrial function and cell fate in antiestrogen-sensitive and -resistant breast cancer cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Exploring the Role of BCL2 Interactome in Cancer: A Protein/Residue Interaction Network Analysis.Biology · 2025Article
- Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer.Cancer research · 2023Article
- Sulfatase-2 from Cancer Associated Fibroblasts: An Environmental Target for Hepatocellular Carcinoma?Liver cancer · 2022Article
- In Vitro Anticancer Activity of Methanolic Extract ofMolecules (Basel, Switzerland) · 2022Article
- Review
- Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Exploring new pathways in endocrine-resistant breast cancer.Exploration of targeted anti-tumor therapy · 2022Review
- Nuclear Mechanisms Involved in Endocrine Resistance.Frontiers in oncology · 2021Review
- Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-Oxidative medicine and cellular longevity · 2021Article
- Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Integrin β8 facilitates tumor growth and drug resistance through a Y-box binding protein 1-dependent signaling pathway in bladder cancer.Cancer science · 2020Article
- Recent progress on the role and molecular mechanism of chicken ovalbumin upstream promoter-transcription factor II in cancer.The Journal of international medical research · 2020Review
- Profiling of human lymphocytes reveals a specific network of protein kinases modulated by endurance training status.Scientific reports · 2020Article
- Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer.Scientific reports · 2019Article
- Article
- Streptolysin O derived from Streptococcus pyogenes inhibits RANKL‑induced osteoclastogenesis through the NF‑κB signaling pathway.Molecular medicine reports · 2019Article
- Endocrine Resistance in Hormone Receptor Positive Breast Cancer-From Mechanism to Therapy.Frontiers in endocrinology · 2019Review
- miR-573 regulates cell proliferation and apoptosis by targeting Bax in nucleus pulposus cells.Cellular & molecular biology letters · 2019Article
- ERβ alters the chemosensitivity of luminal breast cancer cells by regulating p53 function.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to endocrine therapies remains a major problem in the management of estrogen receptor-alpha (ER)-positive breast cancer. We show that inhibition of NF-kappaB (p65/RELA), either by overexpression of a mutant IkappaB (IkappaBSR) or a small-molecule inhibitor of NF-kappaB (parthenolide; IC(50)=500 nM in tamoxifen-resistant cells), synergistically restores sensitivity to 4-hydroxytamoxifen (4HT) in resistant MCF7/RR and MCF7/LCC9 cells and further sensitizes MCF-7 and MCF7/LCC1 control cells to 4HT. These effects are independent of changes in either cell cycle distribution or in the level of autophagy measured by inhibition of p62/SQSTM1 expression and cleavage of LC3. NF-kappaB inhibition restores the ability of 4HT to decrease BCL2 expression, increase mitochondrial membrane permeability, and induce a caspase-dependent apoptotic cell death in resistant cells. Each of these effects is reversed by a caspase 8 (CASP8)-specific inhibitor that blocks enzyme-substrate binding. Thus, increased activation of NF-kappaB can alter sensitivity to tamoxifen by modulating CASP8 activity, with consequent effects on BCL2 expression, mitochondrial function, and apoptosis. These data provide significant new insights into how molecular signaling affects antiestrogen responsiveness and strongly suggest that a combination of parthenolide and tamoxifen may offer a novel therapeutic approach to the management of some ER-positive breast cancers.
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