Pharmacokinetic, Antiproliferative and Apoptotic Effects of Phenolic Acids in Human Colon Adenocarcinoma Cells Using In Vitro and In Silico Approaches

Molecules. 2018 Oct 8;23(10):2569. doi: 10.3390/molecules23102569.

Abstract

Colon cancer is the second most common cause of cancer deaths in the USA and Europe. Despite aggressive therapies, many tumors are resistant to current treatment protocols and epidemiological data suggest that diet is a major factor in the etiology of colon cancer. This study aimed to evaluate the antioxidant activity and the influence of 3,4-dihydroxyphenylacetic (3,4-DHPAA), p-coumaric (p-CoA), vanillic (VA) and ferulic (FA) acids on cell viability, cell cycle progression, and rate of apoptosis in human colon adenocarcinoma cells (HT-29). The results showed that all compounds tested reduce cell viability in human colon cancer cells. 3,4-DHPAA promoted the highest effect antiproliferative with an increase in the percentage of cells in G₀/G₁ phase, accompanied by a reduction of cells in G₂/M phase. Cell cycle analysis of VA and FA showed a decrease in the proportion of cells in G0/G₁ phase (10.0 µM and 100.0 µM). p-CoA and FA acids increased the percentage of apoptotic cells and non-apoptotic cells. 3,4-DHPAA seems to be the substance with the greatest potential for in vivo studies, opening thus a series of perspectives on the use of these compounds in the prevention and treatment of colon cancer.

Keywords: cell cytotoxicity; colon cancer; phenolic acid.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / pharmacokinetics
  • 3,4-Dihydroxyphenylacetic Acid / pharmacology
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Computer Simulation
  • Coumaric Acids / pharmacokinetics
  • Coumaric Acids / pharmacology
  • HT29 Cells
  • Humans
  • Hydroxybenzoates / classification
  • Hydroxybenzoates / pharmacokinetics
  • Hydroxybenzoates / pharmacology*
  • Propionates / pharmacokinetics
  • Propionates / pharmacology
  • Vanillic Acid / pharmacokinetics
  • Vanillic Acid / pharmacology

Substances

  • Coumaric Acids
  • Hydroxybenzoates
  • Propionates
  • 3,4-Dihydroxyphenylacetic Acid
  • ferulic acid
  • Vanillic Acid
  • phenolic acid
  • p-coumaric acid