Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines.

Abstract

To investigate the mechanistic basis for the biological properties of anthocyanins, two aglycone anthocyanins [delphinidin (DY) and cyanidin (CY)] were used to examine their effects on cell cycle progression and on induction of apoptosis in human cancer cells (uterine carcinoma and colon adenocarcinoma cells) and in normal human fibroblasts. These compounds differ in the number and position of hydroxyl groups on the beta ring in the molecular structure. Cellular uptake of anthocyanins was confirmed by HPLC analysis and no metabolites were detected. The clonogenic assay showed that CY induces a dose-dependent growth inhibitory effect only in fibroblasts. This effect was confirmed by flow cytometric analysis, showing a significant reduction of cells in S phase. In contrast, DP inhibited cell growth in normal and tumour cell lines. This event is accompanied in fibroblasts by an accumulation of cells in the S phase suggesting a block in the transition from S to G2 phase. On the other hand, in tumour cell lines we observed a reduction of cells in G1 phase, paralleled by the appearance of a fraction of cells with a hypodiploid DNA content, thus demonstrating an apoptotic effect by DP. The occurrence of apoptosis induced by DP was confirmed by morphological and biochemical features, including nuclear condensation and fragmentation, annexin V staining, DNA laddering and poly(ADP-ribose) polymerase-1-proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with DP was significantly lost. The different effects exerted by DP as compared with CY suggest that the presence of the three hydroxyl groups on the beta ring in the molecular structure of DP may be important for its greater biological activity.

• Authors: Maria Claudia Lazzè, Monica Savio, Roberto Pizzala, Ornella Cazzalini, Paola Perucca, Anna Ivana Scovassi, Lucia Anna Stivala, Livia Bianchi
• Journal: Carcinogenesis (Carcinogenesis) Vol. 25 Issue 8 Pg. 1427-33 (Aug 2004) ISSN: 0143-3334 [Print] England
• PMID: 15016660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Anthocyanins
• Coloring Agents
• Propidium
• DNA
• Poly(ADP-ribose) Polymerases

Topics

• Annexin A5 (pharmacology)
• Anthocyanins (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line
• Cell Line, Tumor
• Cell Survival
• Chromatography, High Pressure Liquid
• Coloring Agents (pharmacology)
• DNA (metabolism)
• DNA Fragmentation
• Fibroblasts (metabolism)
• Flow Cytometry
• G1 Phase
• G2 Phase
• HeLa Cells
• Humans
• Membrane Potentials
• Mitochondria (metabolism, pathology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Propidium (pharmacology)
• S Phase
• Time Factors