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Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1

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Abstract

In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81373445 to Y. X. C.) and the Natural Science Foundation of Jilin Province of China (No. 20150101189JC to Y. X. C.).

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Author notes

  1. Cuihua Hu and Xiaolong Chen have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, 130021, China

    Cuihua Hu, Xiaolong Chen, Yibing Huang & Yuxin Chen

  2. College of Life Sciences, Jilin University, Changchun, 130021, China

    Cuihua Hu, Xiaolong Chen, Yibing Huang & Yuxin Chen

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  1. Cuihua Hu
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  2. Xiaolong Chen
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  3. Yibing Huang
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Contributions

Conceived and designed the experiments: CHH and YXC Performed the experiments: CHH and XLC Analyzed the data: CHH, YBH and YXC. Contributed reagents/materials/analysis tools: CHH, YBH and YXC. Wrote the paper: CHH and YXC.

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Correspondence to Yuxin Chen.

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Hu, C., Chen, X., Huang, Y. et al. Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1. Apoptosis 23, 132–142 (2018). https://doi.org/10.1007/s10495-018-1443-1

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  • DOI: https://doi.org/10.1007/s10495-018-1443-1

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