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

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.