Induction of apoptosis by ribosome-inactivating proteins and related immunotoxins

Int J Cancer. 1996 Nov 4;68(3):349-55. doi: 10.1002/(SICI)1097-0215(19961104)68:3<349::AID-IJC13>3.0.CO;2-3.

Abstract

Immunotoxins have been prepared with 3 ribosome-inactivating proteins (RIPs), namely, momordin, pokeweed anti-viral protein from seeds (PAP-S) and saporin, linked to the Ber-H2 monoclonal antibody directed against the CD30 antigen of human lymphocytes. Either the RIPs or the immunotoxins induced apoptosis in the CD30+ L540 cell line, as shown by the morphological aspects of the cells, by the DNA fragmentation visible at the electrophoresis, and by the formation of DNA breaks evidenced by 2 cytofluorometric techniques (propidium-iodide staining and fluoresceine-isothiocyanate conjugate dUTP incorporation). The AC50 (concentration causing apoptosis in 50% of the cells) is in the range 10(-8) to 10(-7) M in the case of RIPs, and 10(-11) to 10(-10) M in the case of the immunotoxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Flow Cytometry
  • Fluorescence
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology
  • Humans
  • Immunotoxins / pharmacology*
  • Ki-1 Antigen / immunology
  • Leucine / metabolism
  • N-Glycosyl Hydrolases*
  • Plant Proteins / pharmacology*
  • Ribosome Inactivating Proteins, Type 1
  • Ribosome Inactivating Proteins, Type 2
  • Ribosomes / drug effects
  • Saporins
  • Tritium
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • DNA, Neoplasm
  • Immunotoxins
  • Ki-1 Antigen
  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 1
  • Ribosome Inactivating Proteins, Type 2
  • Tritium
  • N-Glycosyl Hydrolases
  • Saporins
  • pokeweed antiviral protein
  • Leucine