7,7''-Dimethoxyagastisflavone-induced apoptotic or autophagic cell death in different cancer cells

Phytother Res. 2012 Apr;26(4):528-34. doi: 10.1002/ptr.3583. Epub 2011 Sep 14.

Abstract

7,7''-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus × media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / isolation & purification
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis*
  • Autophagy*
  • Biflavonoids / isolation & purification
  • Biflavonoids / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Caspase 3 / metabolism
  • Cell Survival
  • Chromatography, High Pressure Liquid
  • Enzyme Activation
  • HT29 Cells
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Membrane Potential, Mitochondrial
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Taxoids / isolation & purification
  • Taxus / chemistry

Substances

  • 7,7''-dimethoxyagastisflavone
  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Biflavonoids
  • Biomarkers, Tumor
  • Taxoids
  • baccatin III
  • CASP3 protein, human
  • Caspase 3