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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

Western blot analysis for activated caspase 3 expression to monitor cellular apoptosis in PC9 and HFW cells at the indicated time points.GAPDH served as a loading control.
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pone.0126390.g005: Western blot analysis for activated caspase 3 expression to monitor cellular apoptosis in PC9 and HFW cells at the indicated time points.GAPDH served as a loading control.

Mentions: To investigate the mode of actions of K4R2Nal2-S1 on human cancer cell line (PC9) and human fibroblast (HFW), cells were treated with FITC-labeled K4R2-Nal2-S1. Nucleus was labeled with DAPI, and the blue signal was observed by UV exciting light. The fluorescence distribution of FITC-labeled K4R2-Nal2-S1 on cell membrane was visualized by the inverted fluorescent microscope. Phase-contrast microscopy showed that K4R2-Nal2-S1 treatment induced cellular swelling in PC9 but not in HFW cells (Fig 4a). Moreover, immunofluorescence analysis revealed that FITC-labeled K4R2-Nal2-S1 treatment caused puncta formation on cell membrane in PC9, but not in HFW cells (Fig 4b). Immunoblotting indicated that K4R2-Nal2-S1 treatment activated caspase 3 in PC9 but not in HFW cells, suggesting the involvement of apoptosis in K4R2-Nal2-S1 mediated cell death (Fig 5). Our data suggest that K4R2-Nal2-S1 preferentially binds cancer cells, causing apoptotic cell death.


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)

Western blot analysis for activated caspase 3 expression to monitor cellular apoptosis in PC9 and HFW cells at the indicated time points.GAPDH served as a loading control.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0126390.g005: Western blot analysis for activated caspase 3 expression to monitor cellular apoptosis in PC9 and HFW cells at the indicated time points.GAPDH served as a loading control.
Mentions: To investigate the mode of actions of K4R2Nal2-S1 on human cancer cell line (PC9) and human fibroblast (HFW), cells were treated with FITC-labeled K4R2-Nal2-S1. Nucleus was labeled with DAPI, and the blue signal was observed by UV exciting light. The fluorescence distribution of FITC-labeled K4R2-Nal2-S1 on cell membrane was visualized by the inverted fluorescent microscope. Phase-contrast microscopy showed that K4R2-Nal2-S1 treatment induced cellular swelling in PC9 but not in HFW cells (Fig 4a). Moreover, immunofluorescence analysis revealed that FITC-labeled K4R2-Nal2-S1 treatment caused puncta formation on cell membrane in PC9, but not in HFW cells (Fig 4b). Immunoblotting indicated that K4R2-Nal2-S1 treatment activated caspase 3 in PC9 but not in HFW cells, suggesting the involvement of apoptosis in K4R2-Nal2-S1 mediated cell death (Fig 5). Our data suggest that K4R2-Nal2-S1 preferentially binds cancer cells, causing apoptotic cell death.

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