ArticleCarcinogenesis2014
Beta-naphthoflavone (DB06732) mediates estrogen receptor-positive breast cancer cell cycle arrest through AhR-dependent regulation of PI3K/AKT and MAPK/ERK signaling.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
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- Cacalol Acetate as Anticancer Agent: Antiproliferative, Pro-Apoptotic, Cytostatic, and Anti-Migratory Effects.Current issues in molecular biology · 2024Article
- The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024Review
- Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells.Frontiers in oncology · 2024Article
- Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review).Molecular medicine reports · 2024Review
- Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15.Nature communications · 2023Article
- Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells.Biochemistry and biophysics reports · 2023Article
- Aryl Hydrocarbon Receptor as an Anticancer Target: An Overview of Ten Years Odyssey.Molecules (Basel, Switzerland) · 2023Review
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- Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest.Current issues in molecular biology · 2022Article
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- β-Naphthoflavone Activation of the Ah Receptor Alleviates Irradiation-Induced Intestinal Injury in Mice.Antioxidants (Basel, Switzerland) · 2020Article
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- GALNT6 promotes breast cancer metastasis by increasing mucin-type O-glycosylation of α2M.Aging · 2020Article
- Emerging roles of aerobic glycolysis in breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Beta-naphthoflavone (BNF, DB06732) is an agonist of aryl hydrocarbon receptor (AhR) and a putative chemotherapeutic agent that has antitumor activity against mammary carcinomas in vivo. However, the mechanism by which BNF exerts this antitumor effect remains unclear. Thus, we explored mechanisms of BNF's antitumor effects in human breast cancer cells. This study showed that BNF suppressed cell proliferation and induced cell cycle arrest in the G0/G1 phase with downregulation of cyclin D1/D3 and CDK4 and upregulation of p21(Cip1/Waf1), leading to a senescence-like phenotype in estrogen receptor (ER)-positive MCF-7 cells, but not in ER-negative MDA-MB-231 cells. In addition, BNF inhibited PI3K/AKT signaling, and the PI3K inhibitor, LY294,002, exhibited the same inhibitory effects on cyclinD1/D3, CDK4 and the cell cycle as BNF. Interestingly, BNF activated mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signaling, and more notably, MEK inhibitor PD98059 significantly blocked the BNF-induced cell cycle arrest and upregulation of p21(Cip1/Waf1). Furthermore, specific ERα and AhR siRNA studies indicate that ERα is required in BNF-induced p21(Cip1/Waf1) expression, and BNF-mediated cell cycle arrest and modulation of AKT and ERK signaling is AhR-dependent. Taken together, AhR-dependent inhibition of the PI3K/AKT pathway, activation of MAPK/ERK and modulation of ERα is a novel mechanism underlying BNF-mediated antitumor effects in breast cancer, which may represent a promising strategy to be exploited in future clinical trials.
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