Iron Modulation Enhances Anticancer Activity of Atorvastatin in SH-SY5Y Neuroblastoma Cells

/aim: Atorvastatin (AT) has cytotoxic effects in SH-SY5Y neuroblastoma cells. However, there is no clear evidence regarding with impact of iron on anticancer efficacy of AT in neuroblastoma cells. This study aimed to explore the effect of AT on viability of SH-SY5Y cells with the presence of iron overload or iron depletion in a cellular environment. SH-SY5Y cells were treated with AT (5, 50 µM) or the test agents, including ferrous sulfate heptahydrate (Fe2S, 300 µM), ferric sulfate hydrate (Fe3S, 300 µM), and deferoxamine (Def, 100 µM), either alone or in combination. Following 24 h of treatment, cell viability (MTT assay), autophagy (acridine orange staining), and intracellular levels of iron, Se, Zn, Cu, Mg, and ferritin levels were determined in SH-SY5Y cells. Co-treatment of SH-SY5Y cells with Def and AT (5 or 50 µM) in the presence of either Fe2S or Fe3S led to a significant reduction in cell viability (P < 0.05). Similarly, a significant decrease in viability was observed when cells were co-treated with AT (50 µM) and Fe2S (P < 0.05). The present findings also suggest that ferritin depletion, impaired AT-induced autophagy, and disturbances in redox balance (reflected by changes in iron, Se, Zn, Cu, and Mg levels) may contribute to the reduced cell viability observed under the experimental conditions. Our results provide evidence that unfavorable iron modulation triggered by excess iron and/or Def as well as redox imbalance could potentiate the anticancer efficacy of AT in SH-SY5Y cells.