A proapoptotic peptide for the treatment of solid tumors.
We have designed a novel peptide, DP1, which is able to mediate significant induction of apoptosis in solid tumors by local injection. This peptide, comprised of a protein transduction domain (PTD), PTD-5, fused to an antimicrobial peptide, (KLAKLAK)2, was able to trigger rapid apoptosis in a variety of cell lines in vitro, including MCA205 murine fibrosarcomas and human head and neck tumors. Furthermore, direct injection of DP1 into day 7 established MCA205 tumors in C57BL/6 mice resulted in the induction of tumor apoptosis and subsequent reduction in tumor volume. These results suggest that DP1 may be used clinically to treat accessible solid tumors or as an adjuvant therapy in conjunction with radiotherapy, standard chemotherapy, immunotherapy, or surgical debulking.
Mai
J C
JC
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Mi
Z
Z
Kim
S H
SH
Ng
B
B
Robbins
P D
PD
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C493735:TFDP1 protein, human; C493736:Tfdp1 protein, mouse; D050680:Transcription Factor DP1; D014157:Transcription Factors; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases