دورية أكاديمية
A pyrazolopyridine as a novel AhR signaling activator with anti-breast cancer properties in vitro and in vivo.
| العنوان: | A pyrazolopyridine as a novel AhR signaling activator with anti-breast cancer properties in vitro and in vivo. |
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| المؤلفون: | Abduh MS; Immune Responses in Different Diseases Research Group, Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: mabdoh@kau.edu.sa., Alwassil OI; Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11451, Saudi Arabia. Electronic address: wassilo@ksau-hs.edu.sa., Aldaqal SM; Immune Responses in Different Diseases Research Group, Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: saldaqal@kau.edu.sa., Alfwuaires MA; Department of Biological Sciences, College of Science, King Faisal University, Hofuf 31982, Saudi Arabia. Electronic address: malfwuaires@kfu.edu.sa., Farhan M; International Medical Research Center (iMReC), Aqaba 77110, Jordan; Drug Development Department, UniTechPharma, Fribourg 1700, Switzerland. Electronic address: mf@unitechpharma.swiss., Hanieh H; International Medical Research Center (iMReC), Aqaba 77110, Jordan; Basic Medical Sciences Department, Faculty of Medicine, Aqaba Medical Sciences University, Aqaba 77110, Jordan. Electronic address: h.hanieh@amsu.edu.jo. |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2024 Apr; Vol. 222, pp. 116079. Date of Electronic Publication: 2024 Feb 23. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| مواضيع طبية MeSH: | Receptors, Aryl Hydrocarbon*/metabolism , Breast Neoplasms*/genetics , Pyrazoles*, Animals ; Mice ; Female ; Humans ; Ligands ; Quality of Life ; Cytochrome P-450 CYP1A1/metabolism ; Pyridines/pharmacology ; Pyridines/therapeutic use ; Aryl Hydrocarbon Receptor Nuclear Translocator/genetics ; SOXC Transcription Factors/metabolism |
| مستخلص: | Breast cancer is one of the main causes of malignancy-related deaths globally and has a significant impact on women's quality of life. Despite significant therapeutic advances, there is a medical need for targeted therapies in breast cancer. Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor mediates responses to environment stimuli, is emerging as a unique pleiotropic target. Herein, a combined molecular simulation and in vitro investigations identified 3-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine (3FPP) as a novel AhR ligand in T47D and MDA-MB-231 breast cancer cells. Its agonistic effects induced formation of the AhR-AhR nuclear translocator (Arnt) heterodimer and prompted its binding to the penta-nucleotide sequence, called xenobiotic-responsive element (XRE) motif. Moreover, 3FPP augmented the promoter-driven luciferase activities and expression of AhR-regulated genes encoding cytochrome P450 1A1 (CYP1A1) and microRNA (miR)-212/132 cluster. It reduced cell viability, migration, and invasion of both cell lines through AhR signaling. These anticancer properties were concomitant with reduced levels of B-cell lymphoma 2 (BCL-2), SRY-related HMG-box4 (SOX4), snail family zinc finger 2 (SNAI2), and cadherin 2 (CDH2). In vivo, 3FPP suppressed tumor growth and activated AhR signaling in an orthotopic mouse model. In conclusion, our results introduce the fused pyrazolopyridine 3FPP as a novel AhR agonist with AhR-specific anti-breast cancer potential in vitro and in vivo. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: AhR agonist; Anticancer effects; Breast cancer; CYP1A1; Cell motility; miR-212/132 cluster |
| المشرفين على المادة: | 0 (Receptors, Aryl Hydrocarbon) 0 (pyrazolopyridine) 0 (Ligands) EC 1.14.14.1 (Cytochrome P-450 CYP1A1) 0 (Pyridines) 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator) 0 (SOX4 protein, human) 0 (SOXC Transcription Factors) 0 (Pyrazoles) |
| تواريخ الأحداث: | Date Created: 20240225 Date Completed: 20240326 Latest Revision: 20240909 |
| رمز التحديث: | 20240910 |
| DOI: | 10.1016/j.bcp.2024.116079 |
| PMID: | 38402910 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2024.116079 |