A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity.
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.
Law
Benedict
B
Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th Street, Room 5406, Charlestown, 02129, USA.
Quinti
Luisa
L
Choi
Yongdoo
Y
Weissleder
Ralph
R
Tung
Ching-Hsuan
CH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D018675:Toxicity Tests; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins