title: 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.
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 24-72 h in the presence of 10-100 µM Gal, Megal, THBA, and malvidin-3-glucoside (M3g). THBA reduced cell viability only at 100 µM, while Gal and Megal (10-100 µM) caused a time- and dose-dependent decrease in cell viability. After 72 h 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.
authors.affiliation: Department of Viticulture and Enology, One Shields Avenue, University of California, Davis.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Forester
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Choy
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Waterhouse
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Oteiza
mesh_terms: D000872:Anthocyanins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000494:pharmacology*; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D001547:Benzaldehydes; D016328:NF-kappa B; D027702:Organic Cation Transporter 1; D050794:STAT1 Transcription Factor; D018808:Transcription Factor AP-1; D005707:Gallic Acid; C025525:3-O-methylgallic acid; C535196:2,4,6-trihydroxybenzaldehyde
keywords: NF-κB, ROS; colon cancer; phenolic acids