The anthocyanin metabolites gallic acid, 3-O-methylgallic acid, and 2,4,6-trihydroxybenzaldehyde decrease human colon cancer cell viability by regulating pro-oncogenic signals

Sarah C. Forester, Ying Y. Choy, Andrew L. Waterhouse, Patricia I. Oteiza

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Anthocyanins are a class of polyphenols abundant in the skins of red grapes, and have been shown to have anti-cancer effects in models of colon cancer [Cooke et al. Int J Cancer 2006;119:2213-2220; Jing et al. J Agric Food Chem 2008;56:9391-9398]. Gut microflora metabolize anthocyanins to phenolic acids and aldehydes. These metabolites may explain the relationship between anthocyanin consumption and reduced incidence of colorectal cancer (CRC). Previously, gallic acid (Gal), 3-O-methylgallic acid (Megal), and 2,4,6-trihydroxybenzaldehyde (THBA) were found to decrease Caco-2 cell viability to a larger extent than other anthocyanin metabolites. To better understand the potential anti-CRC action of these compounds, this paper investigated their capacity to modulate the cell cycle, and induce apoptotic cell death. Dividing Caco-2 cells were incubated for 24-72h in the presence of 10-100μM Gal, Megal, THBA, and malvidin-3-glucoside (M3g). THBA reduced cell viability only at 100μM, while Gal and Megal (10-100μM) caused a time- and dose-dependent decrease in cell viability. After 72h incubation, the metabolites caused cell cycle arrest at G0/G1. The activation of the apoptotic pathway by Megal, Gal, and THBA was evidenced by the activation of caspase-3. However, only Megal and Gal caused DNA fragmentation and nuclear condensation. Megal, Gal, and THBA inhibited transcription factors NF-κB, AP-1, STAT-1, and OCT-1 which are known to be activated in CRC. In conclusion, the anti-cancer effects of Megal and Gal occurs as a consequence of both the inhibition of cell proliferation and induction of apoptosis. The inhibition of transcription factors that promote cell proliferation and survival can in part underlie the observed effects.

Original languageEnglish (US)
Pages (from-to)432-439
Number of pages8
JournalMolecular Carcinogenesis
Volume53
Issue number6
DOIs
StatePublished - 2014

Keywords

  • Colon cancer
  • NF-κB, ROS
  • Phenolic acids

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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