In vitro Characterization of the Rapid Cytotoxicity of Anticancer Peptide HPRP-A2 through Membrane Destruction and Intracellular Mechanism against Gastric Cancer Cell Lines

PLoS One. 2015 Sep 30;10(9):e0139578. doi: 10.1371/journal.pone.0139578. eCollection 2015.

Abstract

In this study, HPRP-A2, a synthetic 15-mer cationic peptides with all D-amino acids, effectively inhibited the survival of gastric cell lines in a dose-dependent manner. Gastric tumor cells killing by HPRP-A2 involves a rapid collapse of the membrane integrity and intracellular pathways. Propidium iodide (PI) and lactate dehydrogenase (LDH) assays demonstrated that one-hour treatment with HPRP-A2 led to membrane permeability changes of BGC-823 cells in a dose-dependent manner. Moreover, HPRP-A2 induced apoptosis in BGC-823 cells involves a marked increase in generation of reactive oxygen species (ROS),caspase-3, -8 and -9 activation, a reduction of mitochondrial membrane potential (MMP), and cell cycle arrest in G1 phase. In addition to its inherent cytotoxicity, HPRP-A2 synergized strongly with doxorubicin (DOX) to enhance the efficacy of killing gastric tumor cells in vitro. We believe that HPRP-A2 with all D-amino acids could be a potent candidate of anticancer therapeutics, especially in combination therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Membrane Permeability / drug effects*
  • Doxorubicin / pharmacology
  • G1 Phase / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / metabolism
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Stomach Neoplasms / drug therapy*

Substances

  • Peptides
  • Reactive Oxygen Species
  • Doxorubicin
  • Caspases

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81373445, YXC and No. 21442001, YBH) and the Natural Science Foundation of Jilin Province (No. 20150101189JC, YC and No. 20140101042JC, YBH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.