دورية أكاديمية
Involvement of ferroptosis in eribulin-induced cytotoxicity in ovarian clear cell carcinoma.
| العنوان: | Involvement of ferroptosis in eribulin-induced cytotoxicity in ovarian clear cell carcinoma. |
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| المؤلفون: | Azumi M; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. Electronic address: azumi@toyaku.ac.jp., Kusama K; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan., Yoshie M; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan., Nakano S; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan., Tsuru A; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan., Kato T; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan; Department of Gynecologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan., Tamura K; Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. Electronic address: hiro@toyaku.ac.jp. |
| المصدر: | European journal of pharmacology [Eur J Pharmacol] 2024 May 15; Vol. 971, pp. 176544. Date of Electronic Publication: 2024 Mar 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : Amsterdam : Elsevier Science Original Publication: Amsterdam, North Holland Pub. Co. |
| مواضيع طبية MeSH: | Ferroptosis* , Carcinoma* , Polyether Polyketides* , Furans* , Ketones*, Humans ; Mice ; Animals ; NF-E2-Related Factor 2/metabolism ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/pharmacology ; Tumor Microenvironment |
| مستخلص: | Ovarian clear cell carcinoma (OCCC) is a unique clinicopathological subtype of epithelial ovarian cancer that is resistant to standard chemotherapy. Eribulin, a microtubule dynamics inhibitor of halichondrin class, has unique effects in the cancer microenvironment such as induction of epithelization and reduction in metastatic potential in breast cancer cells; however, nothing is known about the effect of eribulin and the detailed mechanisms in OCCC. This study aimed to investigate the involvement of ferroptosis and its mechanism in the antitumor activity of eribulin in OCCC cells and a mouse xenograft model. We found that eribulin-induced cell death was reduced by ferroptosis inhibitors; deferoxamine, an iron chelator and ferrostatin-1, a lipid peroxidation inhibitor. Eribulin increased the levels of intracellular iron, reactive oxygen species (ROS), and lipid peroxides, and increased the mitochondrial membrane potential. Eribulin downregulated the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), and superoxide dismutase (SOD) activity. The combination of eribulin and ML210, a glutathione peroxidase 4-inhibiting ferroptosis inducer, had a synergistic effect on ferroptosis. Taken together, our findings show firstly that eribulin triggers ferroptosis in OCCC and this effect occurs via the suppression of the Nrf2-HO-1 signaling pathway, SOD activity and the promotion of lipid peroxidation. These findings suggest that eribulin-induced ferroptosis is associated with its anti-tumor effect and also could be a potential therapeutic target in OCCC. 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 B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Dihydroorotate dehydrogenase; Eribulin; Ferroptosis; Mitochondria; Nrf2; Ovarian clear cell carcinoma |
| المشرفين على المادة: | LR24G6354G (eribulin) 0 (NF-E2-Related Factor 2) 0 (Reactive Oxygen Species) EC 1.15.1.1 (Superoxide Dismutase) 0 (Polyether Polyketides) 0 (Furans) 0 (Ketones) |
| تواريخ الأحداث: | Date Created: 20240329 Date Completed: 20240422 Latest Revision: 20240422 |
| رمز التحديث: | 20240422 |
| DOI: | 10.1016/j.ejphar.2024.176544 |
| PMID: | 38552939 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0712 |
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| DOI: | 10.1016/j.ejphar.2024.176544 |