PMID- 26432335 OWN - NLM STAT- MEDLINE DCOM- 20170210 LR - 20181113 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 37 IP - 3 DP - 2016 Mar TI - Enantiomeric CopA3 dimer peptide suppresses cell viability and tumor xenograft growth of human gastric cancer cells. PG - 3237-45 LID - 10.1007/s13277-015-4162-z [doi] AB - The CopA3 dimer peptide is a coprisin analog that has an anticancer effect against human cancer cells in vitro. In this study, we investigated the anticancer activity of the enantiomeric CopA3 dimer peptide in human gastric cancer cell lines as well as in an in vivo tumor xenograft model. Enantiomeric CopA3 reduced gastric cancer cell viability and exhibited cytotoxicity against cancer cells. Enantiomeric CopA3-induced cell death was mediated by specific interactions with phosphatidylserine and phosphatidylcholine, membrane components that are enriched in cancer cells, in a calcein leakage assay. Moreover, acridine orange/ethidium bromide staining, flow cytometric analysis, and Western blot analysis showed that enantiomeric CopA3 induced apoptotic and necrotic gastric cancer cell death. The antitumor effect was also observed in a mouse tumor xenograft model in which intratumoral inoculation of the peptide resulted in a significant decrease in the SNU-668 gastric cancer tumor volume. In addition, periodic acid-Schiff and hematoxylin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed apoptotic and necrotic cell death in tumor masses treated with greater than 150 mug CopA3. Collectively, these results indicate that the enantiomeric CopA3 dimer peptide induces apoptosis and necrosis of gastric cancer cells in vitro and in vivo, indicating that the peptide is a potential candidate for the treatment of gastric cancer, which is a common cause of cancer and cancer deaths worldwide. FAU - Lee, Joon Ha AU - Lee JH AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. FAU - Kim, In-Woo AU - Kim IW AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. FAU - Shin, Yong Pyo AU - Shin YP AD - Division of Life Sciences, Hoseo University, Asan, 31499, South Korea. FAU - Park, Ho Jin AU - Park HJ AD - Division of Life Sciences, Hoseo University, Asan, 31499, South Korea. FAU - Lee, Young Shin AU - Lee YS AD - Division of Life Sciences, Hoseo University, Asan, 31499, South Korea. FAU - Lee, In Hee AU - Lee IH AD - Division of Life Sciences, Hoseo University, Asan, 31499, South Korea. FAU - Kim, Mi-Ae AU - Kim MA AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. FAU - Yun, Eun-Young AU - Yun EY AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. FAU - Nam, Sung-Hee AU - Nam SH AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. FAU - Ahn, Mi-Young AU - Ahn MY AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. FAU - Kang, Dongchul AU - Kang D AD - Ilsong Institute of Life Science, Hallym University, Anyang, 14066, South Korea. FAU - Hwang, Jae Sam AU - Hwang JS AD - Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. hwangjs@korea.kr. LA - eng PT - Journal Article DEP - 20151002 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Antineoplastic Agents) RN - 0 (CopA3 peptide, Copris tripartitus) RN - 0 (Insect Proteins) RN - EC 3.4.22.- (Caspases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antimicrobial Cationic Peptides/chemistry/*pharmacology MH - Antineoplastic Agents/chemistry/pharmacology MH - Apoptosis/drug effects MH - Blotting, Western MH - Caspases/metabolism MH - Cell Line MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - HeLa Cells MH - Humans MH - Insect Proteins/chemistry/*pharmacology MH - Mice, Inbred BALB C MH - Mice, Nude MH - Protein Multimerization MH - Signal Transduction/drug effects MH - Stereoisomerism MH - Stomach Neoplasms/*drug therapy/pathology MH - Tumor Burden/drug effects MH - *Xenograft Model Antitumor Assays OTO - NOTNLM OT - Anticancer peptide OT - Apoptosis OT - D-CopA3 OT - Necrosis OT - Phosphatidylserine EDAT- 2015/10/04 06:00 MHDA- 2017/02/12 06:00 CRDT- 2015/10/04 06:00 PHST- 2015/07/03 00:00 [received] PHST- 2015/09/27 00:00 [accepted] PHST- 2015/10/04 06:00 [entrez] PHST- 2015/10/04 06:00 [pubmed] PHST- 2017/02/12 06:00 [medline] AID - 10.1007/s13277-015-4162-z [pii] AID - 10.1007/s13277-015-4162-z [doi] PST - ppublish SO - Tumour Biol. 2016 Mar;37(3):3237-45. doi: 10.1007/s13277-015-4162-z. Epub 2015 Oct 2.