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Development of a lytic peptide derived from BH3-only proteins

View Article: PubMed Central - PubMed

ABSTRACT

Despite great advances in cancer therapy, drug resistance is a difficult hurdle to overcome that requires development of anticancer agents with novel and effective modes of action. In a number of studies, lytic peptides have shown remarkable ability to eliminate cancer cells through a different way from traditional treatments. Lytic peptides are positively charged, amphiphilic, and are efficient at binding and disrupting the negatively charged cell membrane of cancer cells. In this study, we described the anticancer properties of a lytic peptide that was developed on the basis of the alignment of amphiphilic BH3 peptides. Our results demonstrated that the positive charge and conformation constraint were favourable for efficient cancer cell elimination. Artificial BCL-2 homology 3 peptides (ABH3) exhibited effective anticancer effects against a series of cancer cell lines in vitro and in HeLa human cervical tumour xenografts in vivo. ABH3 induced cell death in an apoptosis-independent manner through the lytic properties of the peptide that caused disruption of cell membrane. Our results showed that charge tuning and conformation constraining in a lytic peptide could be applied to optimise the anticancer activity of lytic peptides. These results also suggest that ABH3 may be a promising beginning for the development of additional lytic peptides as anticancer reagents.

No MeSH data available.


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Anticancer efficacy of ABH3 in vivo. (a) Tumour size of HeLa xenografts. Tumour size was measured by calliper measurements over a period of 2 weeks. (b) Tumour weights of HeLa xenografts. Mice were killed and tumours were resected after the final injection. Error bars represent maximum and minimum; boxes represent the upper and lower quartiles and median; (c) H&E staining of tumour cross-sections from mice treated with control and ABH3. Scale bar, 20 μm. mean±S.D. (n=5).
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fig5: Anticancer efficacy of ABH3 in vivo. (a) Tumour size of HeLa xenografts. Tumour size was measured by calliper measurements over a period of 2 weeks. (b) Tumour weights of HeLa xenografts. Mice were killed and tumours were resected after the final injection. Error bars represent maximum and minimum; boxes represent the upper and lower quartiles and median; (c) H&E staining of tumour cross-sections from mice treated with control and ABH3. Scale bar, 20 μm. mean±S.D. (n=5).

Mentions: To study the anticancer activity of ABH3 in vivo, we injected nude mice with human cervical cancer cells (Hela) and then administered ABH3 or vehicle control. Tumour volume and weights was significantly reduced after treatment of ABH3 for 12 days compared with vehicle control where tumour volume increased dramatically (Figures 5a and b). Histological stains (H&E staining) showed that the cells were densely packed in the tumour tissue of the control mice but that the cell density was significantly reduced in the tumour tissue of ABH3-treated (Figure 5c). Overall, these results demonstrated that ABH3 has a significant antitumor effect in vivo.


Development of a lytic peptide derived from BH3-only proteins
Anticancer efficacy of ABH3 in vivo. (a) Tumour size of HeLa xenografts. Tumour size was measured by calliper measurements over a period of 2 weeks. (b) Tumour weights of HeLa xenografts. Mice were killed and tumours were resected after the final injection. Error bars represent maximum and minimum; boxes represent the upper and lower quartiles and median; (c) H&E staining of tumour cross-sections from mice treated with control and ABH3. Scale bar, 20 μm. mean±S.D. (n=5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979451&req=5

fig5: Anticancer efficacy of ABH3 in vivo. (a) Tumour size of HeLa xenografts. Tumour size was measured by calliper measurements over a period of 2 weeks. (b) Tumour weights of HeLa xenografts. Mice were killed and tumours were resected after the final injection. Error bars represent maximum and minimum; boxes represent the upper and lower quartiles and median; (c) H&E staining of tumour cross-sections from mice treated with control and ABH3. Scale bar, 20 μm. mean±S.D. (n=5).
Mentions: To study the anticancer activity of ABH3 in vivo, we injected nude mice with human cervical cancer cells (Hela) and then administered ABH3 or vehicle control. Tumour volume and weights was significantly reduced after treatment of ABH3 for 12 days compared with vehicle control where tumour volume increased dramatically (Figures 5a and b). Histological stains (H&E staining) showed that the cells were densely packed in the tumour tissue of the control mice but that the cell density was significantly reduced in the tumour tissue of ABH3-treated (Figure 5c). Overall, these results demonstrated that ABH3 has a significant antitumor effect in vivo.

View Article: PubMed Central - PubMed

ABSTRACT

Despite great advances in cancer therapy, drug resistance is a difficult hurdle to overcome that requires development of anticancer agents with novel and effective modes of action. In a number of studies, lytic peptides have shown remarkable ability to eliminate cancer cells through a different way from traditional treatments. Lytic peptides are positively charged, amphiphilic, and are efficient at binding and disrupting the negatively charged cell membrane of cancer cells. In this study, we described the anticancer properties of a lytic peptide that was developed on the basis of the alignment of amphiphilic BH3 peptides. Our results demonstrated that the positive charge and conformation constraint were favourable for efficient cancer cell elimination. Artificial BCL-2 homology 3 peptides (ABH3) exhibited effective anticancer effects against a series of cancer cell lines in vitro and in HeLa human cervical tumour xenografts in vivo. ABH3 induced cell death in an apoptosis-independent manner through the lytic properties of the peptide that caused disruption of cell membrane. Our results showed that charge tuning and conformation constraining in a lytic peptide could be applied to optimise the anticancer activity of lytic peptides. These results also suggest that ABH3 may be a promising beginning for the development of additional lytic peptides as anticancer reagents.

No MeSH data available.


Related in: MedlinePlus