Induction of apoptosis and inhibition of invasion in human hepatoma cells by anthocyanins from meoru

Ann N Y Acad Sci. 2009 Aug:1171:137-48. doi: 10.1111/j.1749-6632.2009.04689.x.

Abstract

Anthocyanins belong to a class of flavonoids exhibiting antioxidant and anti-inflammatory actions as well as a variety of chemotherapeutic effects. However, little is known about the cellular and molecular mechanism of anticancer activity. In this study, we investigated if the anthocyanins (delphinidin-3,5-diglucoside: cyanidin-3,5-diglucoside: petunidin-3,5-diglucoside: delphinidin-3-glucoside: malvdin-3,5-diglucoside: peonidin-3,5-diglucoside: cyanidin-3-glucoside: petunidin-3-glucoside: peonidin-3- glucoside: malvidin-3- glucoside = 27:63:8.27:1:2.21:2.21:6.7:1.25:5.72:1.25) [corrected] isolated from meoru (Vitis coignetiae Pulliat) exerted antiproliferative and anti-invasive and apoptotic effects on human hepatoma Hep3B cells. It was found that the anthocyanins could inhibit cell growth by 75% at the concentration of 400 microg/mL for 48 h. Flow cytometric analysis showed that the anthocyanins increased the amount of DNA fragments (sub-G1 fraction) in a dose-dependent manner, which is closely related to mitochondrial dysfunction and reduction in antiapoptotic proteins (Bcl-2, xIAP, cIAP-1, and cIAP-2). The anthocyanins also significantly inhibited the migration and invasion of Hep3B cells through a matrigel-coated chamber. Taken together this study indicates that the anthocyanins from meoru have antiproliferative and anti-invasive effects and may induce apoptosis through the activation of the mitochondrial pathway and inhibition of antiapoptotic proteins. This study provides evidence that the anthocyanins isolated from meoru might be useful in the treatment of human hepatitis B-associated hepatoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthocyanins / chemistry
  • Anthocyanins / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Glucosides / pharmacology
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vitis / chemistry*
  • X-Linked Inhibitor of Apoptosis Protein / genetics
  • X-Linked Inhibitor of Apoptosis Protein / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Anthocyanins
  • Glucosides
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • cyanidin-3-O-beta-glucopyranoside
  • peonidin 3-glucoside
  • petunidin-3-glucoside
  • malvidin-3-glucoside