Coadministration of kla peptide with HPRP-A1 to enhance anticancer activity


Autoři: Wenjing Hao aff001;  Cuihua Hu aff003;  Yibing Huang aff001;  Yuxin Chen aff001
Působiště autorů: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China aff001;  School of Life Sciences, Jilin University, Changchun, China aff002;  Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun, China aff003;  International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun, China aff004;  JiangsuProteLight Pharmaceutical & Biotechnology Co., Ltd., Jiangyin, China aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223738

Souhrn

The apoptosis-inducing peptide kla (KLAKLAK)2 possesses the ability to disrupt mitochondrial membranes and induce cancer cell apoptosis, but this peptide has a poor eukaryotic cell-penetrating potential. Thus, it requires the assistance of other peptides for effective translocation at micromolar concentrations. In this study, breast and lung cancer cells were treated by kla peptide co-administrated with membrane-active anticancer peptide HPRP-A1. HPRP-A1 assisted kla to enter cancer cells and localized on mitochondrial membranes to result in cytochrome C releasing and mitochondrial depolarization which ultimately induced apoptosis.The apoptosis rate was up to 65%and 45% on MCF-7 and A549 cell lines, respectively, induced by HPRP-A1 coadministration with kla group. The breast cancer model was constructed in mice, and the anticancer peptides were injected to observe the changes in cancer volume, andimmunohistochemical analysis was performed on the tissues and organs after the drug was administered. Both the weight and volume of tumor tissue were remarkable lower in HPRP-A1 with kla group compared with thosepeptidealonggroups. The results showed that the combined drug group effectively inhibited the growth of cancer and did not cause toxic damage to normal tissues, as well as exhibited significantly improvement on peptide anticancer activity in vitro and in vivo.

Klíčová slova:

Apoptosis – Cancer treatment – Cell membranes – Mitochondria – Mouse models – Polypeptides – Toxicity – Mitochondrial membrane


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2019 Číslo 11