title: Melanoma cell surface-expressed phosphatidylserine as a therapeutic target for cationic anticancer peptide, temporin-1CEa.
abstract: We have previously reported that temporin-1CEa, a cationic antimicrobial peptide, exerts preferential cytotoxicity toward cancer cells. However, the exact molecular mechanism for this cancer-selectivity is still largely unknown. Here, we found that the negatively charged phosphatidylserine (PS) expressed on cancer cell surface serves as a target for temporin-1CEa. Our results indicate that human A375 melanoma cells express 50-fold more PS than non-cancerous HaCaT cells. The expression of cell surface PS in various cancer cell lines closely correlated with their ability to be recognized, bound and killed by temporin-1CEa. Additionally, the cytotoxicity of temporin-1CEa against A375 cells can be ameliorated by annexin V, which binds to cell surface PS with high affinity. Moreover, the data of isothermal titration calorimetry assay further confirmed a direct binding of temporin-1CEa to PS, at a ratio of 1:5 (temporin-1CEa:PS). Interestingly, the circular dichroism spectra analysis using artificial biomembrane revealed that PS not only provides electrostatic attractive sites for temporin-1CEa but also confers the membrane-bound temporin-1CEa to form α-helical structure, therefore, enhances the affinity and membrane disrupting ability of temporin-1CEa. In summary, these findings suggested that the melanoma cells expressed PS may serve as a promising target for temporin-1CEa or other cationic anticancer peptides.
authors.affiliation: a Department of Pharmacy , School of Chemistry and Chemical Engineering, Liaoning Normal University , Dalian , China and.|b Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery , School of Life Science, Liaoning Normal University , Dalian , China.
authors.forename: Che
authors.initials: C
authors.lastname: Wang
authors.affiliation: a Department of Pharmacy , School of Chemistry and Chemical Engineering, Liaoning Normal University , Dalian , China and.
authors.forename: Yin-Wang
authors.initials: YW
authors.lastname: Chen
authors.affiliation: a Department of Pharmacy , School of Chemistry and Chemical Engineering, Liaoning Normal University , Dalian , China and.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: b Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery , School of Life Science, Liaoning Normal University , Dalian , China.
authors.forename: Xian-Ge
authors.initials: XG
authors.lastname: Gong
authors.affiliation: a Department of Pharmacy , School of Chemistry and Chemical Engineering, Liaoning Normal University , Dalian , China and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: b Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery , School of Life Science, Liaoning Normal University , Dalian , China.
authors.forename: De-Jing
authors.initials: DJ
authors.lastname: Shang
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism; D055672:Static Electricity
chemical_list: D017304:Annexin A5; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D010718:Phosphatidylserines; C582109:temporin-1CEa, Rana chensinensis
keywords: Cancer specificity; cationic antimicrobial peptide; melanoma; phosphatidylserine; temporin-1CEa