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Novel antimicrobial peptides with high anticancer activity and selectivity.

Chu HL, Yip BS, Chen KH, Yu HY, Chih YH, Cheng HT, Chou YT, Cheng JW - PLoS ONE (2015)

Bottom Line: We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini.Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death.Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu, 300, Taiwan.

ABSTRACT
We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

No MeSH data available.


Related in: MedlinePlus

K4R2-Nal2-S1 treatment attenuates xenograft tumor growth.(a) Dorsal sides of male nude mice s.c. injected with PC9 human lung cancer cells and i.v. treated with K4R2Nal2-S1 (right) or PBS control (left) at the 46th day after cancer cell implantation (5 days for tumor growth, 40 days for treatment, photographed on the 46th day). (b) Mice body weight (left) and tumor volume (right) from (a) were monitored over the time period as indicated. (c) Exposed tumors (mice were sacrificed at the 46th day after cancer cell implantation) of mice treated with K4R2Nal2-S1 (upper) or PBS (lower). 12 exposed tumors were found in the PBS group (6 mice x 2 side implantation), but only 7 exposed tumors were found in the K4R2Nal2-S1 treatment group. Total tumor weight for both groups were measured and shown in right.
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pone.0126390.g006: K4R2-Nal2-S1 treatment attenuates xenograft tumor growth.(a) Dorsal sides of male nude mice s.c. injected with PC9 human lung cancer cells and i.v. treated with K4R2Nal2-S1 (right) or PBS control (left) at the 46th day after cancer cell implantation (5 days for tumor growth, 40 days for treatment, photographed on the 46th day). (b) Mice body weight (left) and tumor volume (right) from (a) were monitored over the time period as indicated. (c) Exposed tumors (mice were sacrificed at the 46th day after cancer cell implantation) of mice treated with K4R2Nal2-S1 (upper) or PBS (lower). 12 exposed tumors were found in the PBS group (6 mice x 2 side implantation), but only 7 exposed tumors were found in the K4R2Nal2-S1 treatment group. Total tumor weight for both groups were measured and shown in right.

Mentions: To evaluate the anticancer effect of K4R2Nal2-S1 in vivo, PC9 cells were implanted subcutaneously to nude mice (Fig 6a) and followed by K4R2-Nal2-S1 injection via the intravenous route, at a dose of 5 mg/kg, three times weekly (Fig 6b). During the administration, body weight loss was not found in K4R2Nal2-S1 treated group (Fig 6b); however, a significant inhibition in tumor growth was observed in the mice treated with K4R2-Nal2-S1 (Fig 6b). K4R2-Nal2-S1 treatment also decreased the volume and weight of tumors harvested 40 days after injection (Fig 6c).


Novel antimicrobial peptides with high anticancer activity and selectivity.

Chu HL, Yip BS, Chen KH, Yu HY, Chih YH, Cheng HT, Chou YT, Cheng JW - PLoS ONE (2015)

K4R2-Nal2-S1 treatment attenuates xenograft tumor growth.(a) Dorsal sides of male nude mice s.c. injected with PC9 human lung cancer cells and i.v. treated with K4R2Nal2-S1 (right) or PBS control (left) at the 46th day after cancer cell implantation (5 days for tumor growth, 40 days for treatment, photographed on the 46th day). (b) Mice body weight (left) and tumor volume (right) from (a) were monitored over the time period as indicated. (c) Exposed tumors (mice were sacrificed at the 46th day after cancer cell implantation) of mice treated with K4R2Nal2-S1 (upper) or PBS (lower). 12 exposed tumors were found in the PBS group (6 mice x 2 side implantation), but only 7 exposed tumors were found in the K4R2Nal2-S1 treatment group. Total tumor weight for both groups were measured and shown in right.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430538&req=5

pone.0126390.g006: K4R2-Nal2-S1 treatment attenuates xenograft tumor growth.(a) Dorsal sides of male nude mice s.c. injected with PC9 human lung cancer cells and i.v. treated with K4R2Nal2-S1 (right) or PBS control (left) at the 46th day after cancer cell implantation (5 days for tumor growth, 40 days for treatment, photographed on the 46th day). (b) Mice body weight (left) and tumor volume (right) from (a) were monitored over the time period as indicated. (c) Exposed tumors (mice were sacrificed at the 46th day after cancer cell implantation) of mice treated with K4R2Nal2-S1 (upper) or PBS (lower). 12 exposed tumors were found in the PBS group (6 mice x 2 side implantation), but only 7 exposed tumors were found in the K4R2Nal2-S1 treatment group. Total tumor weight for both groups were measured and shown in right.
Mentions: To evaluate the anticancer effect of K4R2Nal2-S1 in vivo, PC9 cells were implanted subcutaneously to nude mice (Fig 6a) and followed by K4R2-Nal2-S1 injection via the intravenous route, at a dose of 5 mg/kg, three times weekly (Fig 6b). During the administration, body weight loss was not found in K4R2Nal2-S1 treated group (Fig 6b); however, a significant inhibition in tumor growth was observed in the mice treated with K4R2-Nal2-S1 (Fig 6b). K4R2-Nal2-S1 treatment also decreased the volume and weight of tumors harvested 40 days after injection (Fig 6c).

Bottom Line: We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini.Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death.Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu, 300, Taiwan.

ABSTRACT
We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

No MeSH data available.


Related in: MedlinePlus