Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target

Archives of Toxicology
Siva Kumar KolluriS H Safe

Abstract

The aryl hydrocarbon receptor (AhR) was initially identified as the receptor that binds and mediates the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related halogenated aromatics. Other toxic compounds including some polynuclear aromatic hydrocarbons act through the AhR; however, during the last 25 years, it has become apparent that the AhR plays an essential role in maintaining cellular homeostasis. Moreover, the scope of ligands that bind the AhR includes endogenous compounds such as multiple tryptophan metabolites, other endogenous biochemicals, pharmaceuticals and health-promoting phytochemicals including flavonoids, indole-3-carbinol and its metabolites. It has also been shown that like other receptors, the AhR is a drug target for multiple diseases including cancer, where both AhR agonists and antagonists effectively block many of the critical hallmarks of cancer in multiple tumor types. This review describes the anti-cancer activities of AhR ligands and demonstrates that it is time to separate the AhR from TCDD and exploit the potential of the AhR as a novel target for cancer chemotherapy.

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Citations

Oct 9, 2018·Journal of Applied Toxicology : JAT·Amir ShadboorestanMohammad Hossein Ghahremani
Jun 7, 2019·The Journal of Biological Chemistry·Un-Ho JinStephen Safe
Apr 8, 2018·Molecular Pharmacology·Martina StepankovaZdenek Dvorak
Oct 30, 2019·Cellular and Molecular Life Sciences : CMLS·Katarzyna WalczakTomasz Plech
Feb 23, 2020·International Journal of Molecular Sciences·Thu Ha PhamFarzad Pakdel
Jun 20, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shumin GuoJian Zhang
May 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ji-Woo KimHan-Jin Park
Dec 21, 2018·Archives of Toxicology·Timothy E HoffmanWilliam H Hanneman
Mar 1, 2019·International Journal of Molecular Sciences·Udo JeschkeVincent Cavaillès
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Dec 31, 2019·Oxidative Medicine and Cellular Longevity·Seung Eun LeeJongsung Lee
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Sep 17, 2020·International Journal of Molecular Sciences·Stephen SafeArul Jayaraman
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Jan 3, 2021·Journal of Applied Genetics·Damian Brauze
Aug 3, 2019·European Journal of Medicinal Chemistry·Lucia BiasuttoMario Zoratti
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Feb 11, 2021·International Journal of Molecular Sciences·Jinyun ChenWilliam K Chan
Feb 17, 2021·The Science of the Total Environment·Diana A StavrevaGordon L Hager

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Methods Mentioned

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xenograft
myristoylation
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