Induction of apoptosis by 2,3-dehydrosilybin via a caspase-dependent pathway in human HeLa cells

Biosci Biotechnol Biochem. 2014;78(2):255-62. doi: 10.1080/09168451.2014.885828. Epub 2014 Apr 14.

Abstract

The aim of this study was to investigate the mechanisms involved in the apoptosis of HeLa cells due to 2,3-dehydrosilybin (DHS) treatment. DHS treatment over 24 h significantly inhibited cell viability and induced apoptosis in a dose-dependent manner. It also triggered the cleavage of caspase-8, caspase-9, caspase-3, and PARP, and significantly increased caspase-3 activity in a dose-dependent manner. Moreover, it triggered the depolarization of the mitochondrial membrane potential (Δψm), the release of cytochrome c into the cytosol, the cleavage of Bid, and the downregulation of Bcl-2 in a dose-dependent manner. Furthermore, z-VAD-fmk (a pan-caspase inhibitor) and z-IETD-fmk (a specific caspase-8 inhibitor) abolished the DHS-induced activation of the caspase-8, -9, and -3, cleavage of PARP, the depolarization of Δψm, the release of cytochrome c, the cleavage of Bid, and the downregulation of Bcl-2. Taken together, these results suggest that DHS-induced apoptosis is mediated by a caspase-dependent pathway in human HeLa cells.

Keywords: 2,3-dehydrosilybin; apoptosis; caspase; cytochrome c; mitochondrial membrane potential (Δψm).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Caspase Inhibitors / pharmacology
  • Caspases / metabolism*
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Down-Regulation / drug effects
  • Enzyme Activation / drug effects
  • HeLa Cells
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Proteolysis / drug effects
  • Silybin
  • Silymarin / pharmacology*

Substances

  • Antineoplastic Agents
  • BH3 Interacting Domain Death Agonist Protein
  • Caspase Inhibitors
  • Silymarin
  • Silybin
  • Cytochromes c
  • Caspases