Sulforaphane-mediated induction of a phase 2 detoxifying enzyme NAD(P)H:quinone reductase and apoptosis in human lymphoblastoid cells

Acta Biochim Pol. 2004;51(3):711-21.

Abstract

The effect of sulforaphane on human lymphoblastoid cells originating from a patient of a high cancer risk was studied. Sulforaphane (SFN) is a naturally occurring substance of chemopreventive activity. In our study, changes in cell growth, induction of apoptosis and phase 2 enzymes as well as glutathione level were examined. Apoptosis was tested by confocal microscopy at three stages: change in mitochondrial membrane potential, caspase activation and phosphatidylserine externalization. We show that SFN increases the activity of the detoxification system: it increases quinone reductase activity at low concentration (0.5-1 microM) and raises glutathione level in a dose-dependent manner. At higher doses (2.5-10 microM) sulforaphane is a cell growth modulator, as it caused cell growth cessation (IC50 = 3.875 microM), and apoptosis inducer. The results obtained suggest that sulforaphane acts as a chemopreventive agent in human lymphoblastoid cells.

MeSH terms

  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Line
  • Enzyme Induction / drug effects
  • Glutathione / metabolism
  • Humans
  • Inactivation, Metabolic
  • Isothiocyanates
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Lymphocytes / enzymology*
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • Phosphatidylserines / metabolism
  • Thiocyanates / chemistry
  • Thiocyanates / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • Phosphatidylserines
  • Thiocyanates
  • NAD(P)H Dehydrogenase (Quinone)
  • Caspases
  • sulforafan
  • Glutathione