Trimetazidine Enhances the Cytotoxicity of Cisplatin in HeLa Cells: An in vitro Study on a Potential Synergistic Drug Interaction
Abstract
Cisplatin is a potent chemotherapeutic agent, yet its clinical utility is often limited by systemic toxicity. Trimetazidine dihydrochloride (TMZ), a metabolic regulator used in cardiovascular medicine, has shown potential in modulating cellular stress and energy metabolism. The efficacy of TMZ against the HeLa cervical cancer cell line has not been previously investigated. This study aimed to investigate the cytotoxic effects of TMZ, both as a monotherapy and in combination with cisplatin, on HeLa cervical cancer cells and T0063 healthy human liver fibroblast cells. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay at 24, 48, and 72 hours. Cells were treated with varying concentrations (1-200 µM) of TMZ and cisplatin. The Selectivity Index (SI) was calculated to assess the differential impact on cancerous versus healthy cells. TMZ monotherapy exhibited negligible cytotoxicity across all time points (IC50 > 200 µM). Cisplatin monotherapy showed time-dependent cytotoxicity in HeLa cells. For combination treatments, the cell line- and time-specific fixed IC₅₀ doses of cisplatin were co-administered with varying concentrations of TMZ (1–200 µM). The co-administration of TMZ and cisplatin at 24 and 48 hours significantly enhanced cytotoxic activity in HeLa cells while simultaneously reducing cytotoxicity in T0063 cells. At 24 hours, the combination treatment increased the SI from 2.66 (cisplatin alone) to 9.91. Similar potential synergistic interaction and cytoprotective trends were observed at 48 hours; however, this synergy diminished by 72 hours. These findings provide the first evidence that TMZ potentiates the efficacy of cisplatin in HeLa cells while preserving the viability of healthy liver cells. TMZ represents a promising candidate for drug repurposing in combination treatments.
Keywords
Cervical cancer, Cytotoxicity, HeLa, MTT, Trimetazidine
Supporting Institution
Ethical Statement
References
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