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Molecular and Cellular Biochemistry

, Volume 400, Issue 1–2, pp 77–86 | Cite as

Antimicrobial peptide GW-H1-induced apoptosis of human gastric cancer AGS cell line is enhanced by suppression of autophagy

  • Wei-Ru Pan
  • Yi-Lin Sophia Chen
  • Hui-Chen Hsu
  • Wei-Jung Chen
Article

Abstract

Gastric cancer is one of the most common malignant cancers worldwide. Due to its poor prognosis and high mortality rate, development of an effective therapeutic method is of urgent need. It has been reported that antimicrobial peptides (AMPs), also known as host-defense peptides, can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity, without harming normal cells or causing severe drug resistance. We have designed a series of novel cationic AMPs with potent antimicrobial activity against a broad spectrum of bacterial pathogens. In the current study, we evaluated their anticancer potency toward gastric cancer AGS cell line. Cell viability assay revealed that GW-H1 exhibited the lowest IC50 value (less than 20 μM). Flow cytometry showed that upon GW-H1 treatment for 0–24 h, apoptotic cell populations of AGS increased in a dose- and time-dependent manner. Western blot analysis further revealed that upon treatment for 2–6 h, apoptosis-related caspases-3, 7, 8, 9, and PARP were cleaved and activated, while autophagy-related LC3-II and beclin-1 were concomitantly increased. These results indicated that both apoptosis and autophagy were involved in the early stage of GW-H1-induced AGS cell death. However, upon treatment for 12–24 h, LC3-II began to decrease and cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provided support for future application of GW-H1 as a potential anticancer agent for gastric cancer treatment.

Keywords

Antimicrobial peptides Gastric cancer Apoptosis Autophagy 

Notes

Acknowledgments

Grant sponsor: National Science Council of Taiwan. Grant numbers: NSC 100-2311-B-197-001 and NSC 101-2311-B-197-001.

Conflict of interest

No competing financial interests exist.

Supplementary material

11010_2014_2264_MOESM1_ESM.docx (177 kb)
Supplementary material 1 (DOCX 177 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Wei-Ru Pan
    • 1
  • Yi-Lin Sophia Chen
    • 1
  • Hui-Chen Hsu
    • 1
  • Wei-Jung Chen
    • 1
  1. 1.Department of Biotechnology and Animal ScienceNational Ilan UniversityIlanTaiwan, ROC

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