The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
- breast cancer cell context which includes differential expression of the ER and other as yet unidentified factors,
- breast cancer complexity associated with multiple classifications of tumors based on differences in their histopathology, gene expression, and other clinical parameters,
- ligand structure and the fact that selective AhR modulators (SAhRMs) exhibit tissue/cell-specific AhR agonist or antagonist activity,
- other mechanisms of action of the AhR which involve altered genomic and non-genomic (e.g., cell membrane) pathways that may be differentially be affected by AhR ligands some of which also activate more than one receptor. An example of dual receptor ligands are the polyaromatic hydrocarbons (PAHs) and other compounds which bind both the AhR and ER [36,37,38,39].
2. Selective AhR Modulators (SAhRMs)
3. AhR in Breast Cancer: Prognostic Significance
4. Role of the AhR and Its Ligands as Inhibitors Breast Cancer in Cellular and Rodent Models
5. AhR and AhR Ligands Enhance Mammary Carcinogenesis
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Compounds | Responses | Cell | KO | In Vivo | Reference |
---|---|---|---|---|---|
TCDD | multiple | MDA-MB-231 MDA-MB-436 MDA-MB-157 MDA-MB-435 and BT474 | ✓ | [73] | |
2,3,7,8-TCDF | multiple | MDA-MB-231 MDA-MB-436 MDA-MB-157 MDA-MB-435 and BT474 | ✓ | [73] | |
2,3,4,7,8-PeCDD | multiple | MDA-MB-231 MDA-MB-436 MDA-MB-157 MDA-MB-435 and BT474 | ✓ | [73] | |
1,2,3,7,8-PeCDD | multiple | MDA-MB-231 MDA-MB-436 MDA-MB-157 MDA-MB-435 and BT474 | ✓ | [73] | |
3,3′4,4′,5-PeCB | multiple | MDA-MB-231 MDA-MB-436 MDA-MB-157 MDA-MB-435 and BT474 | ✓ | [73] | |
TCDD | cell cycle prog. | MCF-7 | – | – | [82] |
TCDD | gr. | MDA-MB-468 | – | ✓ | [83] |
TCDD | gr. | MCF-7 | – | – | [84] |
TCDD | CXCR4/CXCL12 | Multiple | [85] | ||
TCDD | Inv | MDA-MB-231, SKBR3 | ✓ | – | [79] |
TCDD | Inv | MDA-MB-231, SKBR3 | ✓ | – | [79] |
TCDD | Inv | MDA-MB-231, T47D | ✓ | – | [86] |
TCDD | Inv | MDA-MB-231 and BT474 | ✓ | – | [87] |
TCDD | gr | MCF-7 | – | ✓ | [88] |
TCDD | met | 4T-1 | – | ✓ | [89] |
Compounds | Responses | Cells | KO | In Vivo | Reference |
---|---|---|---|---|---|
MCDF | gr | MDA-MB-453, MDA-MB-436, HCC-38, MDA-MB-435, BT-474, MDA-MB-157 | ✓ | [73] | |
MCDF | inv | MDA-MB-231 and BT474 | ✓ | ✓ | [87] |
MCDF | gr | MDA-MB-468 | – | ✓ | [83] |
Aminoflavone | gr, DNA damage cytotoxicity, ROS apoptosis | MCF-7, MDA-MB-231, T47D. ZR-75, MDA-MB-468 | – | ✓ | [24,25,26,90,91,92,93,94,95] |
Aminobenzothiazoles (DF-203 and SF-203) | gr, ROS, DNA damage | MCF-7, MDA-MB-468, CRL2335, MDA-MB-435 | – | ✓ | [96,97,98,99,100,101,102,103] |
Naphthylamide der-invatives (NAP6) | gr | MCF-7, MDA-MB-231, BT26, BT474, MDA-MB-468 | – | ✓ | [104,105] |
#12 (quinazoline derivative) | gr, apoptosis, MMP, ROS | MCF-7 | – | ✓ | [106] |
ANI -7 (acrylo-nitriles) | gr | MCF-7, T47D, ZR-75 SKBR3, MDA-MB-468, BT20, and BT474 | ✓ | – | [107,108,109] |
Aminoglycoside CG3-15943 | MDA-MB-468 | ✓ | – | [110,111] | |
Flutamide | migr. | MDA-MB-468 | – | – | [54] |
Leflunomide | migr. | MDA-MB-468 | – | – | [54] |
Nimodipine | migr. | MDA-MB-468 | – | – | [54] |
Omeprazole | migr. | MDA-MB-468 | – | – | [54] |
Sulindac | migr. | MDA-MB-468 | – | – | [54] |
Sulindac | migr | MDA-MB-468 | – | – | [54] |
Tranilast | inv, migr, gr, met | MDA-MB-468, 4T1 | – | ✓ | [54,113,114,115] |
β-Naphthoflavone | gr | MCF-7, MDA-MB-231 | ✓ | – | [116] |
Raloxifene | Apoptosis | MDA-MB-231 | ✓ | – | [117] |
Carbidopa | multiple | MCF-7, MDA-MB-231 | ✓ | [112] | |
4-Hydroxytamoxifen | diff | MCF-7 | – | – | [118] |
Compounds | Responses | Cells | KO | In vivo | Reference |
---|---|---|---|---|---|
DIM | gr, invasion, met | MDA-MB-231, MCF-7, 4T-1 | ✓ | ✓ | [78,86,119,120,121,122] |
I3C | gr, migr. apoptosis | MIF-7, MDA-MB-231, MDA-MB-468, T47D | – | – | [123,124,125,126] |
ICZ | migr | MCF-7, MDA-MB-231, | – | – | [125] |
Luteolin | inv, gr, met | MDA-MB-231 | – | – | [129] |
Icaritin MIR-212/132 | gr | MCF-7 | ✓ | ✓ | [130] |
Flavipin | gr, inv, migr | MDA-MB-231, T47D | ✓ | ✓ | [131] |
Glyceollins CI and II | migr | MDA-MB-231 | – | – | [132] |
Camalexin | gr, migr (mammosphere) | MCF-7, T47D | – | ✓ | [133] |
2-Hydroxy-6-tridecylbenzone acia | gr | MDA-MB-231 | – | – | [134] |
Gallic acid | apoptosis, migr, inv, gr | T47D, MDA-MB-231 | [135] | ||
ITE | MCF7, MDA-MB-231. MDA-MB-157 | ✓ | – | [136] | |
FICZ | gr, migr | MCF-7 | ✓ | – | [137] |
Indoxylsulfate | ROS, met, migr | 4T1 | ✓ | – | [138] |
Indolepropionic acid | gr, ROS, met | 4T1, SKBR3 | ✓ | – | [139] |
Compound | Responses/Pathway | Cells | KO | In Vivo | Reference |
---|---|---|---|---|---|
TCDD | gr, Myc/Rel-AhR | Hs5787 | – | – | [30,140] |
FICZ, BaP, TCDD, XA, Kyn | migr/AhR-TDO-Kyn | SUM149, Hs578T | ✓ | ✓ | [141] |
CB7993113 DMBA | migr, inv, tox | BP1, Hs5787 | ✓ | – | [142] |
FICZ, BaP, TCDD | migr/AhR-SOX2 | Hs578T, MCF-7,SUM149 | ✓ | – | [144] |
Galangin, NF, MC | gr/genes | Hs5787 | ✓ | – | [143] |
DIM, TCDD | colony form, migr | BP1, Hs578T, SUM149, MDA-MB-231 | ✓ | – | [31,145] |
Kyn | colonies, inv met/AhR-TDO-KYN, NFkB | BT59, SUM159, MDA-MB-231 | ✓ | – | [146] |
BaP | inv, gr, migr | MDA-MB-231 | ✓ | – | [147] |
Phthalates | migr, inv/HDAC6 | MCF-7, MDA-MB-231 | ✓ | – | [148,149,150] |
TCDD, Kyn | surv, infl/COX2, NFkB | MDA-MB-231, SKBR3, others | ✓ | – | [151] |
MC | cytotox/AKR1C3 | MDA-MB-231 | ✓ | – | [152] |
TCDD | apoptosis, gr, AhRR | MDA-MB-231, MCF-7, others | ✓ | – | [153] |
CH223191 | Proangiogenic/AhR-AREG-ROS | multiple | ✓ | ✓ | [154] |
CH223191 | met, migr, motility | MDA-MB-231, Hs578T Others | ✓ | ✓ | [155] |
MC | gr/AhR-GPER | SKBR3 | ✓ | – | [156] |
TCDD, BaP | infl, IL6 | MCF-7 | ✓ | – | [157] |
MC | migr/HRG-AhR | MCF-7 | ✓ | – | [158] |
5-Hydroxtryptophan | IL-2-CD8 +T cell exhaustion | 4T1 | ✓ | ✓ | [159] |
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Safe, S.; Zhang, L. The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer. Cancers 2022, 14, 5574. https://doi.org/10.3390/cancers14225574
Safe S, Zhang L. The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer. Cancers. 2022; 14(22):5574. https://doi.org/10.3390/cancers14225574
Chicago/Turabian StyleSafe, Stephen, and Lei Zhang. 2022. "The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer" Cancers 14, no. 22: 5574. https://doi.org/10.3390/cancers14225574
APA StyleSafe, S., & Zhang, L. (2022). The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer. Cancers, 14(22), 5574. https://doi.org/10.3390/cancers14225574