دورية أكاديمية
Everolimus prevents doxorubicin-induced apoptosis in H9c2 cardiomyocytes but not in MCF-7 cancer cells: Cardioprotective roles of autophagy, mitophagy, and AKT.
| العنوان: | Everolimus prevents doxorubicin-induced apoptosis in H9c2 cardiomyocytes but not in MCF-7 cancer cells: Cardioprotective roles of autophagy, mitophagy, and AKT. |
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| المؤلفون: | Kanno SI; Department of Clinical Pharmacotherapeutics, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address: syu-kan@tohoku-mpu.ac.jp., Hara A; Department of Clinical Pharmacotherapeutics, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. |
| المصدر: | Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Dec; Vol. 93, pp. 105698. Date of Electronic Publication: 2023 Sep 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 8712158 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3177 (Electronic) Linking ISSN: 08872333 NLM ISO Abbreviation: Toxicol In Vitro Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford ; New York : Pergamon Press, c1987- |
| مواضيع طبية MeSH: | Cardiotoxicity*/prevention & control , Doxorubicin*/adverse effects , Doxorubicin*/toxicity , Everolimus*/pharmacology , Myocytes, Cardiac*/drug effects , Neoplasms*/metabolism, Animals ; Humans ; Rats ; Apoptosis ; Autophagy ; MCF-7 Cells ; Mitophagy ; Oxidative Stress ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction |
| مستخلص: | Cardiotoxicity is a severe side effect of the chemotherapeutic agent doxorubicin (DOX). We recently showed that DOX-induced cardiomyocyte apoptosis and death were attenuated through autophagy pre-induction. Herein, we assessed how the autophagy/mitophagy-inducing antitumor drug everolimus (EVL) affected DOX-induced cytotoxicity in the rat cardiomyocyte cell line H9c2 and human breast cancer cell line MCF-7. Apoptosis was assessed using annexin V assay. Autophagy and mitophagy were assessed using fluorescence assays. Cellular protein levels were determined using western blotting. Pretreatment with EVL (1 nM) before DOX exposure inhibited mammalian target of rapamycin (mTOR) activity, induced autophagy and mitophagy, and activated protein kinase B (AKT) in H9c2 cells. In mitochondria, DOX (1 μM) induced structural damage (decreased membrane potential and release of cytochrome c), increased superoxide levels, decreased apoptosis inhibitor Bcl-2, and increased apoptosis inducer Bax, leading to apoptosis and reduced viability in H9c2 cells. EVL pretreatment suppressed DOX-induced changes. EVL anti-apoptotic effects were inhibited by treatment with MK-2206, a selective AKT inhibitor. Furthermore, EVL suppressed DOX-induced cardiotoxicity through autophagy/mitophagy and AKT activation but did not attenuate DOX-induced apoptosis or reduction in viability in MCF-7 cells. Altogether, EVL can protect cardiomyocytes from DOX-induced apoptosis and toxicity without reducing DOX antitumor effects, allowing safer chemotherapy. Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose. (Copyright © 2023. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: Apoptosis; Autophagy; Cardiomyocyte; Cytotoxicity; Doxorubicin; Everolimus |
| المشرفين على المادة: | 80168379AG (Doxorubicin) 9HW64Q8G6G (Everolimus) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20230922 Date Completed: 20231103 Latest Revision: 20231103 |
| رمز التحديث: | 20231104 |
| DOI: | 10.1016/j.tiv.2023.105698 |
| PMID: | 37739323 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-3177 |
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| DOI: | 10.1016/j.tiv.2023.105698 |