| Title | A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity. |
| Publication Type | Journal Article |
| Year of Publication | 2006 |
| Authors | Law B, Quinti L, Choi Y, Weissleder R, Tung C-H |
| Journal | Mol Cancer Ther |
| Volume | 5 |
| Issue | 8 |
| Pagination | 1944-9 |
| Date Published | 2006 Aug |
| ISSN | 1535-7163 |
| Keywords | Animals, Antineoplastic Agents, Apoptosis, Cells, Cultured, Drug Screening Assays, Antitumor, Female, Humans, Inhibitory Concentration 50, Kinetics, Mice, Mice, Nude, Mitochondria, Peptides, Recombinant Fusion Proteins, Toxicity Tests, Xenograft Model Antitumor Assays |
| Abstract | A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC(50) of r7-kla (3.54 +/- 0.11 micromol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within minutes, the morphologic changes in cells and mitochondrial leakage were apparent by microscopy and was consistent with rapid apoptosis. Our results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems. |
| DOI | 10.1158/1535-7163.MCT-05-0509 |
| Alternate Journal | Mol Cancer Ther |
| PubMed ID | 16928814 |
| Grant List | P50-CA86355 / CA / NCI NIH HHS / United States R01 CA99385 / CA / NCI NIH HHS / United States |
Related Institute:
Molecular Imaging Innovations Institute (MI3)