Adenovirus infection enhances killing of melanoma cells by a mitotoxin.
Toxins are effective in cell killing if internalized efficiently. Conjugation of the plant toxin saporin with basic fibroblast growth factor has increased tumor killing due to better internalization, but toxin uptake by cells has remained relatively inefficient. We show here that infection of melanoma cells with a replication-defective adenovirus enhances cell killing by the mitotoxin basic fibroblast growth factor-saporin more than 10-fold, thus allowing tumor cell killing in vivo at nontoxic concentrations. Adenovirus infection leads to increased apoptosis by the mitotoxin due to enhanced internalization of the ligand-receptor complex and release of the active toxin from the endosomes.
Satyamoorthy
K
K
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Soballe
P W
PW
Soans
F
F
Herlyn
M
M
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000257:Adenoviridae Infections / Q000503:physiopathology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D051379:Mice; D009699:N-Glycosyl Hydrolases; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000494:pharmacology* / Q000633:toxicity; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins