Curcumin inhibits growth of Saccharomyces cerevisiae through iron chelation

Eukaryot Cell. 2011 Nov;10(11):1574-81. doi: 10.1128/EC.05163-11. Epub 2011 Sep 9.

Abstract

Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G(1) phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Copper / metabolism
  • Curcumin / pharmacology*
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Iron / analysis
  • Iron / metabolism*
  • Iron Chelating Agents / pharmacology*
  • Mutation
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism

Substances

  • Iron Chelating Agents
  • Copper
  • Iron
  • Curcumin