caa a22 4500 606236546 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2264-3 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2264-3 Antimicrobial peptide GW-H1-induced apoptosis of human gastric cancer AGS cell line is enhanced by suppression of autophagy [Elektronische Daten] [Wei-Ru Pan, Yi-Lin Chen, Hui-Chen Hsu, Wei-Jung Chen] 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 20μM). Flow cytometry showed that upon GW-H1 treatment for 0-24h, apoptotic cell populations of AGS increased in a dose- and time-dependent manner. Western blot analysis further revealed that upon treatment for 2-6h, 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 12-24h, 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. Springer Science+Business Media New York, 2014 Antimicrobial peptides nationallicence Gastric cancer nationallicence Apoptosis nationallicence Autophagy nationallicence Pan Wei-Ru Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut Chen Yi-Lin Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut Hsu Hui-Chen Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut Chen Wei-Jung Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 77-86 0300-8177 400:1-2<77 2015 400 11010 https://doi.org/10.1007/s11010-014-2264-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2264-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pan Wei-Ru Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut NATIONALLICENCE 700 1- Chen Yi-Lin Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut NATIONALLICENCE 700 1- Hsu Hui-Chen Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut NATIONALLICENCE 700 1- Chen Wei-Jung Department of Biotechnology and Animal Science, National Ilan University, 1 Shen-Lung Road Sec.1, 26047, Ilan, Taiwan, ROC aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 77-86 0300-8177 400:1-2<77 2015 400 11010