Copper-induced non-monotonic dose response in Caco-2 cells

Abstract

Copper is an essential dietary micronutrient in humans for proper cell function; however, in excess, it is toxic. The human cell line Caco-2 is popular as an in vitro model for intestinal absorption and toxicology. This study investigated the response of exponentially growing Caco-2 cells to prolonged copper exposure (120 h). An unexpected non-monotonic dose-response profile was observed in Caco-2 cells. Exposure to media supplemented with 3.125 μM CuSO4 resulted in decreased cell yield vs. untreated. However, toxicity was progressively reduced from 90% at 3.125 μM to 60% at 25 μM. This effect was documented between 48 and 120 h continuous exposure (p < 0.05). This triphasic toxicity curve was observed to be specific to copper in Caco-2 cells, as iron, manganese and zinc displayed monotonic dose-response profiles. Two inorganic copper forms, copper sulphate and copper chloride, were shown to conserve the non-monotonic dose-response curve. The triphasic effect was shown to be specific to Caco-2 cells. These results have implications for research investigating the effect of copper and other micronutrients using Caco-2 cells.

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Funding

This work was funded by a joint Enterprise Ireland Innovative Partnership programme (IP/2015/0375).

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Correspondence to Charles O’Doherty.

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Editor: Tetsuji Okamoto

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O’Doherty, C., Keenan, J., Horgan, K. et al. Copper-induced non-monotonic dose response in Caco-2 cells. In Vitro Cell.Dev.Biol.-Animal 55, 221–225 (2019). https://doi.org/10.1007/s11626-019-00333-8

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Keywords

  • Dose response
  • Copper
  • Caco-2
  • Triphasic
  • Trace elements
  • Toxicity