Induction of apoptosis in human papillomaviruspositive cancer cells by peptide aptamers targeting the viral E6 oncoprotein.
Certain types of human papillomaviruses (HPVs) are closely linked to the development of human cancers. Herein, it is shown that intracellular targeting of the HPV16 E6 oncoprotein by E6-binding peptide aptamers resulted in the apoptotic elimination of HPV16-positive cancer cells, whereas HPV-negative cells were not affected. These results provide direct experimental evidence that the HPV E6 oncoprotein has antiapoptotic activity in HPV-positive tumor cells that is required for their survival. The E6-targeting molecules identified herein have implications for the development of therapeutic strategies for the treatment of HPV-associated dysplasias and cancers.
Butz
K
K
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
Denk
C
C
Ullmann
A
A
Scheffner
M
M
Hoppe-Seyler
F
F
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000187:drug effects*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012097:Repressor Proteins
D000970:Antineoplastic Agents; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D010455:Peptides; D012097:Repressor Proteins