Synergistic Induction of Oxidative Stress – Mediated Cell Death in HeLa cervical cancer cells by Dapagliflozin- Albendazole Mixture | ||
| Egyptian Journal of Histology | ||
| Articles in Press, Accepted Manuscript, Available Online from 28 October 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejh.2025.431977.2342 | ||
| Authors | ||
| Youssef Shakuri Yasin* 1; Ayat Ali Salih2; Marwah Isam Sulaiman Musa2; Henan Dh . Skheel Aljebori3; Azal Hamoody Jumaa4 | ||
| 1Bilad Alrafidain University, Iraq. | ||
| 2Department of biology, College of education for pure sciences, Tikrit University, Iraq. | ||
| 3College of Medicine , Al Mustansiriyah University, Iraq. | ||
| 4Iraqi National Cancer Research Center/the University of Baghdad , Iraq. | ||
| Abstract | ||
| Objective: This in vitro study was conducted to assess the cytotoxic effects and selective induction of oxidative stress by the (Dapagliflozin – Albendazole) mixture on HeLa cervical cancer cells, compared to normal human foreskin fibroblasts (HFF). Materials and Methods: The cytotoxic effects of individual pharmacological agents and their combinations were evaluated in HeLa and HFF cell lines via the MTT assay. Drug interactions were quantified utilizing the Combination Index (CI) and the Dose Reduction Index (DRI). Oxidative stress parameters, including glutathione (GSH) depletion, superoxide anion production, and lipid peroxidation evidenced by malondialdehyde (MDA) levels, were assessed. Furthermore, molecular docking simulations were performed to predict the binding affinities of the drugs to metabolic enzyme targets, specifically Glucose-6-Phosphate Dehydrogenase (G6PD) and mitochondrial Complex I. Results: The mixture showed potent, synergistic cytotoxicity (CI < 1) against HeLa cells, with a significantly reduced IC50 of 6.84 µg/mL at 72 hours. It displayed a highly favorable selectivity index compared to cisplatin. Mechanistically, the mixture caused oxidative stress. Albendazole increased mitochondrial superoxide production, while Dapagliflozin decreased GSH levels. This synergy resulted in a substantial increase in lipid peroxidation, indicated by higher MDA levels. These effects were minimally observed in normal human foreskin fibroblast (HFF) cells. The molecular docking study confirmed these findings, showing high-affinity interactions of Dapagliflozin with G6PD, with docking scores of -8.1 kcal/mol. Similarly, Albendazole strongly bound to mitochondrial Complex I, with docking scores of -7.2 kcal/mol. Conclusion: The Dapagliflozin-Albendazole combination synergistically induces selective oxidative catastrophe in cervical cancer cells by concurrently elevating reactive oxygen species and disabling antioxidant defenses, presenting a promising repurposed therapy with a wide therapeutic window. | ||
| Keywords | ||
| Dapagliflozin and Albendazole; Synergistic Cytotoxicity; Oxidative Stress; Cervical Cancer; Drug Repurposing | ||
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