A phenylacetaldehyde-flavonoid adduct, 8-C-(E-phenylethenyl)-norartocarpetin, exhibits intrinsic apoptosis and MAPK pathways-related anticancer potential on HepG2, SMMC-7721 and QGY-7703

Food Chem. 2016 Apr 15:197 Pt B:1085-92. doi: 10.1016/j.foodchem.2015.11.104. Epub 2015 Nov 27.

Abstract

Norartocarpetin, quercetin and naringenin were found to effectively inhibit 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation through trapping its phenylacetaldehyde and form their adducts in roast beef patties. Six adducts [8-C- or 6-C-(E-phenylethenyl) flavonoids] formed between phenylacetaldehyde and three flavonoids were detected in roast beef patties by UPLC-MS analyses and compared with their synthetic references. These flavonoid-phenylacetaldehyde adducts were synthesised and further subjected to cytotoxicity tests on three liver cancer cell lines HepG2, SMMC-7721 and QGY-7703. The adduct 8-C-(E-phenylethenyl)norartocarpetin (NARA1) was found to significantly induce cancer cell death with IC50 values about 7 μM. After pre-treating with MAPK and caspase inhibitors, alteration of the cell morphology and cleaved-PARP were detected in liver cancer cell lines administered with NARA1. These data indicated that norartocarpetin could inhibit PhIP formation in roast beef patties and form norartocarpetin-phenylacetaldehyde adducts. The adduct NARA1 has anticancer potential via intrinsic caspase-dependent and cell context-dependent MAPKs pathways.

Keywords: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); Cytotoxicity effects; Flavonoids; Flavonoid–phenylacetaldehyde adducts; Phenylacetaldehyde.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / analogs & derivatives
  • Acetaldehyde / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Flavonoids / analysis
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Food Handling
  • Hep G2 Cells
  • Humans
  • Imidazoles / metabolism
  • Liver Neoplasms / drug therapy
  • MAP Kinase Signaling System / drug effects*
  • Red Meat / analysis

Substances

  • 8-C-(E-phenylethenyl)-norartocarpetin
  • Antineoplastic Agents
  • Flavonoids
  • Imidazoles
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Acetaldehyde
  • phenylacetaldehyde