دورية أكاديمية
Enhanced in vivo targeting of estrogen receptor alpha signaling in murine mammary adenocarcinoma by nilotinib/rosuvastatin novel combination.
| العنوان: | Enhanced in vivo targeting of estrogen receptor alpha signaling in murine mammary adenocarcinoma by nilotinib/rosuvastatin novel combination. |
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| المؤلفون: | Goda AE; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. Electronic address: AHMEDELSAYEDGODA@pharm.tanta.edu.eg., Elsisi AE; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt., Sokkar SS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt., Abdelrazik NM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. |
| المصدر: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2020 Oct 01; Vol. 404, pp. 115185. Date of Electronic Publication: 2020 Aug 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0333 (Electronic) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | Adenocarcinoma/*veterinary , Estrogen Receptor alpha/*antagonists & inhibitors , Mammary Neoplasms, Animal/*drug therapy , Pyrimidines/*therapeutic use , Rosuvastatin Calcium/*therapeutic use, Adenocarcinoma/drug therapy ; Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Mammary Neoplasms, Experimental/drug therapy ; Mice ; Pyrimidines/administration & dosage ; Rosuvastatin Calcium/administration & dosage |
| مستخلص: | The development of resistance to endocrine therapy of estrogen receptor alpha (ERα)-positive breast cancer is inevitable, necessitating the introduction of alternative treatment strategies. Therefore, the current study was carried out to investigate the in vivo efficacy and tolerability of nilotinib/rosuvastatin novel combination against ERα-positive breast carcinoma. Results showed that treatment of tumor-bearing mice with nilotinib/rosuvastatin exerted a significant antitumor activity. Mechanistically, the combination treatment efficiently inhibited the in vivo ERα protein expression, whereas ERα mRNA levels were unaffected suggesting a posttranslational regulation. In addition, the combination treatment markedly downregulated the expression of two ERα downstream target genes: C3 and pS2 confirming the inhibition of ERα signaling in vivo. Further, nilotinib/rosuvastatin combination strongly induced apoptosis evidenced by a marked caspase-3 cleavage and downregulation of tumor nitric oxide levels. Moreover, histopathology showed significant declines in mitotic figures and tumor giant cells implying the in vivo capability of the combination treatment to interfere with cancer cell proliferation and persistence. Of note, the combination treatment abrogated nilotinib-induced hypercholesterolemia and did not adversely affect the liver function or body weight. Overall, the present study provided evidences that warrant further assessment of nilotinib/rosuvastatin combination as an alternative therapeutic modality for ERα-positive breast cancer. 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 © 2020 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Apoptosis; Breast cancer; Estrogen receptor alpha; Nilotinib; Rosuvastatin |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Estrogen Receptor alpha) 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) 0 (Pyrimidines) 83MVU38M7Q (Rosuvastatin Calcium) F41401512X (nilotinib) |
| SCR Disease Name: | Adenocarcinoid tumor |
| تواريخ الأحداث: | Date Created: 20200811 Date Completed: 20210106 Latest Revision: 20220114 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.taap.2020.115185 |
| PMID: | 32771489 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0333 |
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| DOI: | 10.1016/j.taap.2020.115185 |