Crocin and quercetin prevent PAT-induced apoptosis in mammalian cells: Involvement of ROS-mediated ER stress pathway

Environ Toxicol. 2016 Dec;31(12):1851-1858. doi: 10.1002/tox.22185. Epub 2015 Aug 27.

Abstract

Patulin (PAT) is a secondary metabolite produced by several species of the genera of Penicillium, Aspergillus, and Byssochlamys that can be found in rotting fruits, especially in apples and apple-based products. Exposure to this mycotoxin has been reported to induce intestinal and kidney injuries. The mechanism underlying such toxicity has been linked to the induction of apoptosis which occurred with reactive oxygen species production and endoplasmic reticulum (ER) stress induction. This study aimed to evaluate the effect of the two common dietary compounds Quercetin (QUER), a natural flavonoid, and Crocin (CRO), a natural carotenoid, on PAT-induced toxicity in human colon carcinoma (HCT116) and embryonic kidney cells (HEK293). We showed that antioxidant properties of QUER and CRO help to prevent ER stress activation and lipid peroxidation as evidenced by the reduction in GRP78 and GADD34 expressions and the decrease in malondialdehyde production. Furthermore, we demonstrated their ability to re-establish the loss of the mitochondrial membrane potential to inhibit caspase 3 activation and DNA fragmentation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1851-1858, 2016.

Keywords: Patulin; apoptosis; endoplasmic reticulum stress; oxidative stress.

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Carotenoids / pharmacology*
  • Caspase 3 / metabolism
  • DNA Fragmentation / drug effects
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects*
  • Enzyme Activation
  • HCT116 Cells
  • HEK293 Cells
  • Heat-Shock Proteins / metabolism
  • Humans
  • Lipid Peroxidation / drug effects
  • Malondialdehyde / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Patulin / toxicity*
  • Protein Phosphatase 1 / metabolism
  • Quercetin / pharmacology*
  • Reactive Oxygen Species / metabolism*

Substances

  • Antioxidants
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Reactive Oxygen Species
  • Carotenoids
  • Malondialdehyde
  • crocin
  • Patulin
  • Quercetin
  • PPP1R15A protein, human
  • Protein Phosphatase 1
  • Caspase 3