Boric Acid Suppresses Cell Survival by Triggering Endoplasmic Reticulum Stress-Induced Autophagy in Cervical Cancers

Sep 23, 2026

Cervical cancer is the fourth most common cancer among women globally. This study evaluates how boric acid affects endoplasmic reticulum (ER) stress and autophagy signaling in cervical cancer cells. Cell viability and proliferation were assessed in HUF and HeLa lines, followed by cyclin D1/CDK4 and nuclear morphology analyses. Autophagosome formation and ER stress/autophagy marker expression were measured in HeLa cells. Results show IC50 differences, G1 arrest in HeLa, enhanced autophagy and ER stress, and increased apoptosis-related markers, supporting potential therapeutic effects through ER stress and autophagy regulation.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Introduction

Background on cervical cancer

Endoplasmic reticulum stress and UPR pathways

Journal of Cellular and Molecular Medicine ORIGINAL ARTICLE OPEN ACCESS Boric Acid Suppresses Cell Survival by Triggering Endoplasmic Reticulum Stress-Induced Autophagyin Cervical Cancers Betul Keyif1 | Ceyhan Hacioglu2,3 1Faculty of Medicine, Department of Gynecology and Obstetrics, Düzce University, Düzce, Turkey | 2Faculty of Medicine, Department of Medical Biochemistry, Düzce University, Düzce, Turkey | 3Faculty of Pharmacy, Department of Biochemistry, Düzce University, Düzce, Turkey Correspondence: Ceyhan Hacioglu ([ceyhanhacioglu@duzce.edu.tr](ceyhanhacioglu@duzce.edu.tr)) Received: 8 February 2025 | Revised: 20 June 2025 | Accepted: 10 July 2025 Keywords: autophagy | boric acid | cervical cancer | endoplasmic reticulum stress 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. 1 | Introduction Cervical cancer ranks as the fourth most common malignancy affecting women globally, both in terms of incidence and mortality [1] . It is a prevalent and aggressive tumour of the female reproductive system, characterised by its high malignancy and rapid progression [2] . In 2018 alone, approximately 570,000 women were diagnosed with cervical cancer, and 311,000 succumbed to the disease worldwide [3] . While mortality rates vary significantly between countries, cervical cancer remains the leading cause of cancer-related deaths amongst women in low-income nations [4] . The primary etiological factor linked to cervical cancer is infection with the human papillomavirus (HPV) [5]. Currently, doctors primarily treat early-stage cervical cancer through surgery; however, patients with high-risk factors and those with intermediate to advanced stages typically require radiotherapy and chemotherapy [6] . Despite standardised treatment protocols, significant challenges remain in the management of cervical cancer. Notably, there is a pressing need to develop therapeutic strategies that minimise side effects and reduce harm to the human body. The endoplasmic reticulum (ER) is a versatile organelle responsible for the biosynthesis of secretory, transmembrane and cytosolic proteins, as well as lipids [7]. To ensure proper protein folding, the ER contains high concentrations of chaperone proteins that assist in the correct folding of newly synthesised proteins [8]. Various cellular stressors can interfere with the ER's synthesis and This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is prop

FAQs

What was the main goal of the study on boric acid in cervical cancer cells?

To investigate how boric acid influences endoplasmic reticulum (ER) stress and autophagy signaling pathways in cervical cancer cells.

How did boric acid affect cell viability in HUF versus HeLa cells?

Boric acid showed an IC50 of 3.17 mM in HUF cells, while it was significantly lower at 641.2 μM in HeLa cells, indicating higher sensitivity in HeLa cells.

What mechanisms did the study link to boric acid’s effects in HeLa cells?

It promoted autophagy by increasing autophagosome formation and upregulating Beclin1, p62, and LC3, while simultaneously inducing ER stress through increased GRP78 and downstream UPR markers, and increasing apoptotic signals via cleaved-caspase-3.

Sep 23, 2026

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