title: Antitumor activity of opiorphin, sialorphin and their conjugates with a peptide klaklakklaklak.
abstract: This is the study on the effect of opiorphin, sialorphin and their analogs on antitumor activity. We demonstrated that conjugation of opiorphin and sialorphin with a proapoptotic, antimicrobial peptide klak (klaklakklaklak) led to compounds (opio-klak and sialo-klak) that were cytotoxic against cancer cells (LN18, PC3, A549, HCT116 and B10-F16) in the MTT test. The conjugated analogs were designed to increase the effectiveness of the peptide. The opio-klak derivative was the most effective in the in vitro assays and led to a decrease in viability of cancer cells over time as compared with that of untreated controls. In contrast, treatment with either the untargeted klak peptide or opiorphin as a negative control led to a negligible loss in viability. Antitumor effect of the opio-klak was also observed in vivo in murine melanoma tumor-bearing mice. Cessation of peptide administration resulted in tumor regrowth. Our results are seemingly valuable for the development of opiorphin analogs with potential clinical applications. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: University of Gdansk, Faculty of Chemistry, Gdansk, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kamysz
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Smolarczyk
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cichoń
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jarosz-Biej
authors.affiliation: University of Gdansk, Faculty of Chemistry, Gdansk, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikorska
authors.affiliation: University of Gdansk, Faculty of Chemistry, Gdansk, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sobocińska
authors.affiliation: Medical University of Gdansk, Faculty of Pharmacy, Gdansk, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Jaśkiewicz
authors.affiliation: Medical University of Gdansk, Faculty of Pharmacy, Gdansk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011498:Protein Precursors / Q000138:chemical synthesis / Q000494:pharmacology*; D012471:Salivary Proteins and Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D060327:Solid-Phase Synthesis Techniques; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D009842:Oligopeptides; D011498:Protein Precursors; D012471:Salivary Proteins and Peptides; C066861:Smr3b protein, rat; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine
keywords: antitumor activity; circular dichroism; melanoma; opiorphin; peptide synthesis; sialorphin