pelargonidin and Liver-Neoplasms

We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells. AhR-dependent reporter gene expression in transfected HepG2 cells was increased by pelargonidin in a concentration-dependent manner at 24h. Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR. CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Ligand binding analysis demonstrated that pelargonidin was a weak ligand of AhR. Enzyme kinetic analyses using human liver microsomes revealed inhibition of CYP1A1 activity by delphinidin (IC50 78 μM) and pelargonidin (IC50 33 μM). Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity.

Topics: Anthocyanins; Basic Helix-Loop-Helix Transcription Factors; Cytochrome P-450 CYP1A1; Dose-Response Relationship, Drug; Enzyme Induction; Hep G2 Cells; Hepatocytes; Humans; Intestinal Neoplasms; Kinetics; Ligands; Liver Neoplasms; Microsomes, Liver; Polychlorinated Dibenzodioxins; Primary Cell Culture; Promoter Regions, Genetic; Receptors, Aryl Hydrocarbon; RNA, Messenger; Signal Transduction; Transcriptional Activation; Transfection

Antioxidant extracts from 5 potato lines were evaluated for antioxidant activity, total phenolics, chlorogenic acid, anthocyanin content, and in vitro anticancer capacity. Analysis showed that Mexican wild species S. pinnatisectum had the highest antioxidant activity, total phenolic, and chlorogenic acid content. The proliferation of colon cancer and liver cancer cells was significantly inhibited by potato antioxidant extracts. The highest antiproliferative activity was observed in extracts of S. pinnatisectum and the lowest in Northstar. An inverse correlation was found between total phenolics and the EC(50) of colon cancer cell (R(2) = 0.9303), as well as liver cancer cell proliferation (R(2) = 0.8992). The relationship between antioxidant activity and EC(50) of colon cancer/liver cancer cell proliferation was significant (R(2) = 0.8144; R(2) = 0.956, respectively). A significant difference in inhibition of cancer cells (P < 0.01) existed between the 3 polyphenols: chlorogenic acid, pelargonidin chloride, and malvidin chloride, suggesting that chlorogenic acid was a critical factor in the antiproliferation of colon cancer and liver cancer cells.

Topics: Anthocyanins; Anticarcinogenic Agents; Antioxidants; Caco-2 Cells; Cell Proliferation; Chlorogenic Acid; Hep G2 Cells; Humans; Liver Neoplasms; Lung Neoplasms; Plant Extracts; Polyphenols; Solanum tuberosum