title: Enantiomeric CopA3 dimer peptide suppresses cell viability and tumor xenograft growth of human gastric cancer cells.
abstract: 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 μg 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.
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
authors.forename: In-Woo
authors.initials: IW
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Hoseo University, Asan, 31499, South Korea.
authors.forename: Yong Pyo
authors.initials: YP
authors.lastname: Shin
authors.affiliation: Division of Life Sciences, Hoseo University, Asan, 31499, South Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Life Sciences, Hoseo University, Asan, 31499, South Korea.
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Life Sciences, Hoseo University, Asan, 31499, South Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Yun
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Nam
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Ahn
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, 14066, South Korea.
authors.forename: Dongchul
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea. hwangjs@korea.kr.
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055503:Protein Multimerization; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C583724:CopA3 peptide, Copris tripartitus; D019476:Insect Proteins; D020169:Caspases
keywords: Anticancer peptide; Apoptosis; D-CopA3; Necrosis; Phosphatidylserine