Camalexin, an indole phytoalexin, inhibits cell proliferation, migration, and mammosphere formation in breast cancer cells via the aryl hydrocarbon receptor

2021 ◽  
Author(s):  
Naoya Yamashita ◽  
Chiharu Taga ◽  
Moeno Ozawa ◽  
Yuichiro Kanno ◽  
Noriko Sanada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammosphere Formation ◽  
Aryl Hydrocarbon

scholarly journals Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Travis B. Salisbury ◽  
Gary Z. Morris ◽  
Justin K. Tomblin ◽  
Ateeq R. Chaudhry ◽  
Carla R. Cook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Aryl Hydrocarbon

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P<0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity.

scholarly journals The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Mariana A. Callero ◽  
Andrea I. Loaiza-Pérez
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Agents ◽  
Breast Cancers ◽  
Nude Mouse Model ◽  
Aryl Hydrocarbon ◽  
Mcf 7

Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.

scholarly journals An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER−/PR−/Her2− Human Breast Cancer Cells

2016 ◽  
Vol 90 (5) ◽  
pp. 674-688 ◽  
Author(s):  
Olga Novikov ◽  
Zhongyan Wang ◽  
Elizabeth A. Stanford ◽  
Ashley J. Parks ◽  
Alejandra Ramirez-Cardenas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Aryl Hydrocarbon ◽  
Amplification Loop

scholarly journals The aryl hydrocarbon receptor (AhR) mediates resistance to apoptosis induced in breast cancer cells

2015 ◽  
Vol 120 ◽  
pp. 5-13 ◽  
Author(s):  
Kanae Bekki ◽  
Helena Vogel ◽  
Wen Li ◽  
Tomohiro Ito ◽  
Colleen Sweeney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Aryl Hydrocarbon

scholarly journals Aryl Hydrocarbon Receptor Activates NDRG1 Transcription under Hypoxia in Breast Cancer Cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
En-Yu Li ◽  
Wei-Yung Huang ◽  
Ya-Chu Chang ◽  
Mong-Hsun Tsai ◽  
Eric Y. Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Aryl Hydrocarbon

scholarly journals Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1018
Author(s):  
Julia Hohenbichler ◽  
Georg Aichinger ◽  
Michael Rychlik ◽  
Giorgia Del Favero ◽  
Doris Marko
Keyword(s):  
Breast Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Binary Mixtures ◽  
Alternaria Alternata ◽  
Breast Cancer Cells ◽  
Receptor Activation ◽  
Alternariol Monomethyl Ether ◽  
Aryl Hydrocarbon ◽  
Erod Assay

Alternaria molds simultaneously produce a large variety of mycotoxins, of which several were previously reported to induce enzymes of phase I metabolism through aryl hydrocarbon receptor activation. Thus, we investigated the potential of naturally occurring Alternaria toxin mixtures to induce Cytochrome P450 (CYP) 1A1/1A2/1B1 activity. Two variants of an extract from cultured Alternaria alternata, as well as the toxins alternariol (AOH), alternariol monomethyl ether (AME), altertoxin I (ATX-I), and altertoxin II (ATX-II), were tested singularly and in binary mixtures applying the 7-ethoxy-resorufin-O-deethylase (EROD) assay in MCF-7 breast cancer cells. Sub-cytotoxic concentrations of the two toxin mixtures, as well as ATX-I, ATX-II and AOH, exhibited dose-dependent enhancements of CYP 1 activity. ATX-I and ATX-II interacted synergistically in this respect, demonstrating the two perylene quinones as major contributors to the extract’s potential. Binary mixtures between AOH and the two altertoxins respectively exhibited concentration-dependent antagonistic as well as synergistic combinatory effects. Notably, AME showed no efficacy towards EROD enzyme activity or impact on other toxins’ efficacy. Hence, this study provides insights into synergistic and other combinatory effects of Alternaria toxins in natural co-occurrence scenarios in the context of AhR signalling pathway activation in breast cancer cells.

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