Resveratrol Causes Arrest in the S-phase Prior to Fas-independent Apoptosis in CEM-C7H2 Acute Leukemia Cells

Cell Death Differ. 2000 Sep;7(9):834-42. doi: 10.1038/sj.cdd.4400719.

Abstract

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), in the concentration range of 20 microM and above, induced arrest in the S-phase and apoptosis in the T cell-derived T-ALL lymphocytic leukemia cell line CEM-C7H2 which is deficient in functional p53 and p16. Expression of transgenic p16/INK4A, which causes arrest in G0/G1, markedly reduced the percentage of apoptotic cells. Antagonist antibodies to Fas or FasL, or constitutive expression of crmA did not diminish the extent of resveratrol-induced apoptosis. Furthermore, a caspase-8-negative, Fas-resistant Jurkat cell line was sensitive to resveratrol-induced apoptosis which could be strongly inhibited in the Jurkat as well as in the CEM cell line by z-VAD-fmk and z-IETD-fmk. The almost complete inhibition by z-IETD-fmk and the lack of inhibition by crmA suggested caspase-6 to be the essential initiator caspase. Western blots revealed the massive conversion of procaspase-6 to its active form, while caspase-3 and caspase-2 were proteolytically activated to a much lesser extent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antibodies, Monoclonal / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase Inhibitors*
  • Caspases / metabolism
  • Cell Separation
  • Dose-Response Relationship, Drug
  • Doxycycline / pharmacology
  • Fas Ligand Protein
  • Flow Cytometry
  • Humans
  • Interphase / drug effects
  • Jurkat Cells
  • Leukemia-Lymphoma, Adult T-Cell
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Resveratrol
  • S Phase / drug effects*
  • Stilbenes / pharmacology*
  • Time Factors
  • Transfection
  • Transgenes / genetics
  • Tumor Cells, Cultured
  • fas Receptor / metabolism*

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Antineoplastic Agents, Phytogenic
  • Caspase Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Stilbenes
  • fas Receptor
  • Caspases
  • Doxycycline
  • Resveratrol