Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells.
The chicken anemia virus protein apoptin induces a p53-independent, Bcl-2-insensitive type of apoptosis in various human tumor cells. Here, we show that, in vitro, apoptin fails to induce programmed cell death in normal lymphoid, dermal, epidermal, endothelial, and smooth-muscle cells. However, when normal cells are transformed they become susceptible to apoptosis by apoptin. Long-term expression of apoptin in normal human fibroblasts revealed that apoptin has no toxic or transforming activity in these cells. In normal cells, apoptin was found predominantly in the cytoplasm, whereas in transformed and malignant cells it was located in the nucleus, suggesting that the localization of apoptin is related to its activity. These properties make apoptin a potential agent for the treatment of a large number of tumors, also those lacking p53 and/or overexpressing Bcl-2.
Danen-Van Oorschot
A A
AA
Laboratory for Molecular Carcinogenesis, Sylvius Laboratory, Leiden University, P.O. Box 9503, 2300 RA Leiden, The Netherlands.
Fischer
D F
DF
Grimbergen
J M
JM
Klein
B
B
Zhuang
S
S
Falkenburg
J H
JH
Backendorf
C
C
Quax
P H
PH
Van der Eb
A J
AJ
Noteborn
M H
MH
D017209:Apoptosis; D002213:Capsid / Q000032:analysis / Q000096:biosynthesis*; D036022:Capsid Proteins; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D017727:Chicken anemia virus / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D013539:Simian virus 40; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D036022:Capsid Proteins; D011994:Recombinant Proteins; C091717:VP3 protein, Chicken anemia virus