Anticancer effects of CAMEL peptide.
This study analyzed whether therapy with CAMEL, an antimicrobial peptide (KWKLFKKIGAVLKVL), possess anticancer benefits. Although the peptide was cytotoxic for all the cell lines tested, it did not cause hemolysis, which suggests that CAMEL does not damage cell membranes. After cellular internalization, CAMEL localized to mitochondria and lowered the mitochondrial potential, resulting in the organelles' swelling, a decrease in cellular ATP level and, finally, cellular breakdown. High mobility group box 1 (HMGB1) protein, a necrotic death marker, was shown to be released from cells treated with CAMEL. Growth of B16-F10 melanoma tumors was clearly restrained after injections with CAMEL and could be kept in check throughout the period of peptide administration. However, if therapy was stopped, tumors started to grow again 3-4 days later. To reduce tumor volume and block tumor relapse, a combined therapy was required involving CAMEL and plasmid DNA carrying the interleukin-12 (IL-12) gene. The two therapeutic agents used in combination (a series of CAMEL injections first, followed by daily administration of plasmid DNA) delayed tumor growth and extended survival of treated animals in a statistically significant manner. Complete tumor regression was found in 60% of cases.
Smolarczyk
Ryszard
R
Department of Molecular Biology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. rsmolarczyk@io.gliwice.pl
Cichoń
Tomasz
T
Kamysz
Wojciech
W
Głowala-Kosińska
Magdalena
M
Szydło
Anna
A
Szultka
Lukasz
L
Sieroń
Aleksander L
AL
Szala
Stanisław
S
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D009842:Oligopeptides; D007770:L-Lactate Dehydrogenase