دورية أكاديمية
Parthenolide repressed endometriosis induced surgically in rats: Role of PTEN/PI3Kinase/AKT/GSK-3β/β-catenin signaling in inhibition of epithelial mesenchymal transition.
| العنوان: | Parthenolide repressed endometriosis induced surgically in rats: Role of PTEN/PI3Kinase/AKT/GSK-3β/β-catenin signaling in inhibition of epithelial mesenchymal transition. |
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| المؤلفون: | Kabil SL; Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Egypt. Electronic address: SLKabel@medicine.zu.edu.eg., Rashed HE; Department of Pathology, Faculty of Medicine, Zagazig University, Egypt. Electronic address: Herashed@zu.edu.eg., Mohamed NM; Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Egypt. Electronic address: NMMohamed@pnu.edu.sa., Elwany NE; Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Egypt. Electronic address: NAAlwan@medicine.zu.edu.eg. |
| المصدر: | Life sciences [Life Sci] 2023 Oct 15; Vol. 331, pp. 122037. Date of Electronic Publication: 2023 Aug 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Endometriosis*/drug therapy , Sesquiterpenes*/pharmacology, Humans ; Rats ; Female ; Animals ; beta Catenin/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Epithelial-Mesenchymal Transition ; Vimentin/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; Cadherins/metabolism ; Cell Movement ; PTEN Phosphohydrolase/metabolism |
| مستخلص: | Aim: PI3K/AKT/GSK-3β/β-catenin signaling pathway is a triggering factor for epithelial to mesenchymal transition (EMT) which plays a pivotal role in the pathogenesis of endometriosis. Parthenolide is a sesquiterpene lactone extract that has anti-inflammatory, analgesic and anticancer properties. Hence, we investigated the effect of parthenolide against EMT in the endometrial tissue implants and immortalized epithelial endometriotic cell lines 12Z. Main Methods: Twenty- four female Rats with surgically induced endometriosis were treated with parthenolide (2, 4 mg/kg), for 4 weeks. Endometriotic cell line 12Z was used to identify the effect of parthenolide on the wound healing, cellular migration and invasion properties of endometriotic cells. Key Findings: Parthenolide decreased the endometriotic implant tissue expression of total PI3K, PI3K-p85, p-AKT, p/total AKT, p-GSK-3β, P/total GSK-3β, and nβ-catenin, as well as increased E-cadherin and decreased vimentin mRNA expression. Parthenolide upregulated PTEN immunoreactivity as well as the endometriotic tissue caspase-3, caspase-9, BAX levels while reducing Bcl2 level. Additionally, parthenolide decreased endometriotic tissue implants surface area and histopathological score of the epithelial growth. Significance: Our findings showed that parthenolide in a dose dependent manner inhibited PI3K/AKT/GSK-3β/nβ-catenin cascade via enhancement of PTEN with subsequent inhibition of EMT evidenced by elevation of the epithelial marker, E-cadherin and reduction of mesenchymal marker, vimentin, of the endometriotic implants in addition to reversal of invasion and migration properties of epithelial endometriotic cell lines. These findings provide a valuable therapeutic approach for treatment of endometriosis. Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Endometriosis; Epithelial to mesenchymal transition; Parthenolide |
| المشرفين على المادة: | 0 (beta Catenin) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) 0 (Vimentin) 2RDB26I5ZB (parthenolide) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) 0 (Cadherins) 0 (Sesquiterpenes) EC 3.1.3.67 (PTEN protein, human) EC 3.1.3.67 (PTEN Phosphohydrolase) |
| تواريخ الأحداث: | Date Created: 20230826 Date Completed: 20230925 Latest Revision: 20230925 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.lfs.2023.122037 |
| PMID: | 37633416 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0631 |
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| DOI: | 10.1016/j.lfs.2023.122037 |