Induction of apoptosis by ribosome-inactivating proteins and related immunotoxins.
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.
Dipartimento di Patologia Sperimentale, Università Bologna, Italy.
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Bolognesi
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PL
Tazzari
F
F
Olivieri
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L
Polito
B
B
Falini
F
F
Stirpe
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005453:Fluorescence; D006689:Hodgkin Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D017730:Ki-1 Antigen / Q000276:immunology; D007930:Leucine / Q000378:metabolism; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D012270:Ribosomes / Q000187:drug effects; D000076985:Saporins; D014316:Tritium; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D000922:Immunotoxins; D017730:Ki-1 Antigen; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D014316:Tritium; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; C024275:pokeweed antiviral protein; D007930:Leucine