Boric Acid Suppresses Cell Survival by Triggering Endoplasmic Reticulum Stress-Induced Autophagy in Cervical Cancers.
| Title: | Boric Acid Suppresses Cell Survival by Triggering Endoplasmic Reticulum Stress-Induced Autophagy in Cervical Cancers. |
|---|---|
| Authors: | Keyif B; Faculty of Medicine, Department of Gynecology and Obstetrics, Düzce University, Düzce, Turkey.; Hacioglu C; Faculty of Medicine, Department of Medical Biochemistry, Düzce University, Düzce, Turkey.; Faculty of Pharmacy, Department of Biochemistry, Düzce University, Düzce, Turkey. |
| Source: | Journal of cellular and molecular medicine [J Cell Mol Med] 2025 Jul; Vol. 29 (14), pp. e70740. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, England : Wiley-Blackwell; Original Publication: Bucharest : "Carol Davila" University Press, 2000- |
| MeSH Terms: | Endoplasmic Reticulum Stress*/drug effects ; Autophagy*/drug effects ; Boric Acids*/pharmacology ; Uterine Cervical Neoplasms*/pathology ; Uterine Cervical Neoplasms*/metabolism ; Uterine Cervical Neoplasms*/drug therapy ; Uterine Cervical Neoplasms*/genetics; Cell Survival/drug effects ; Cell Proliferation/drug effects ; Cyclin D1/metabolism ; Cyclin D1/genetics ; Apoptosis/drug effects ; Signal Transduction/drug effects ; Cyclin-Dependent Kinase 4/metabolism ; Cyclin-Dependent Kinase 4/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Female ; Endoplasmic Reticulum Chaperone BiP ; HeLa Cells |
| Abstract: | Cervical cancer ranks as the fourth most common cancer amongst women globally. This study aimed to investigate boric acid's effects on endoplasmic reticulum (ER) stress and autophagy signalling pathways in cervical cancer cells. We first assessed boric acid's effects on cell viability and proliferation in HUF and HeLa cell lines. Subsequently, we analysed cyclin D1 and CDK4 levels and boric acid-induced nuclear morphology changes. We then examined autophagosome formation and mRNA expression of autophagy/ER stress markers (Beclin1, p62, LC3-I/II, GRP78, p-IRE1α, p-PERK, CHOP and cleaved-caspase-3) in HeLa cells. The findings revealed that boric acid's IC50 was 3.17 mM for HUF cells but significantly lower (641.2 μM) for HeLa cells, indicating cancer cell sensitivity. In HeLa cells, boric acid-induced a dose-dependent decrease in cyclin D1 and CDK4 levels (associated with G1 phase arrest), which we did not observe in HUF cells. Additionally, boric acid treatment caused nuclear abnormalities in HeLa cells. Boric acid promoted autophagy by enhancing autophagosome formation and upregulating Beclin1, p62, and LC3-I/II expression. Concurrently, it induced ER stress by increasing GRP78, p-IRE1α, p-PERK and CHOP expression. Furthermore, boric acid increased cleaved-caspase-3 expression and apoptotic cell counts. In conclusion, this study underscores boric acid's potential therapeutic effects in cervical cancer through ER stress and autophagy regulation.; (© 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.) |
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| Contributed Indexing: | Keywords: autophagy; boric acid; cervical cancer; endoplasmic reticulum stress |
| Substance Nomenclature: | 0 (Boric Acids); 0 (HSPA5 protein, human); 0 (Endoplasmic Reticulum Chaperone BiP); R57ZHV85D4 (boric acid); 136601-57-5 (Cyclin D1); EC 2.7.11.22 (Cyclin-Dependent Kinase 4) |
| Entry Date(s): | Date Created: 20250719 Date Completed: 20250719 Latest Revision: 20250723 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12274959 |
| DOI: | 10.1111/jcmm.70740 |
| PMID: | 40682482 |
| Database: | MEDLINE |
Journal Article