Anticancer effects of CAMEL peptide

• Published in: Laboratory investigation Vol. 90; no. 6; pp. 940 - 952
• Main Authors: Smolarczyk, Ryszard, Cichoń, Tomasz, Kamysz, Wojciech, Głowala-Kosińska, Magdalena, Szydło, Anna, Szultka, Łukasz, Sieroń, Aleksander L, Szala, Stanisław
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01-06-2010; Nature Publishing Group US; Nature Publishing Group
• Subjects: 631/61/338/22; 631/67/1059; 631/67/1813/1634; 631/92/436/2388; Amino Acid Sequence; Animals; Anti-Bacterial Agents - pharmacology; anticancer therapy; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biotechnology; CAMEL peptide; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - ultrastructure; Cell Membrane - drug effects; Cell Membrane - physiology; Cell Survival - drug effects; combined therapy; Fundamental and applied biological sciences. Psychology; Genetic Therapy - methods; immunotherapy; Investigative techniques, diagnostic techniques (general aspects); Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Kidney Neoplasms - ultrastructure; L-Lactate Dehydrogenase - metabolism; Laboratory Medicine; Medical sciences; Medicine; Medicine & Public Health; Melanoma - drug therapy; Melanoma - pathology; Melanoma - ultrastructure; Melanoma, Experimental - drug therapy; Melanoma, Experimental - enzymology; Melanoma, Experimental - pathology; Melanoma, Experimental - ultrastructure; Mice; necrosis; Oligopeptides - pharmacology; Pathology; research-article; combined therapy; anticancer therapy; CAMEL peptide; necrosis; immunotherapy; Antineoplastic agent; Biotechnology; Peptides; Animal; Immunotherapy; Clinical biology; Combined treatment; Necrosis
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2010.58

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.