title: Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A.
abstract: CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA-N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the testedCandidas(C. glabrata,C. parapsilosis,C. krusei,C. tropicalisandC. albicans) at a concentration of <0.8 mM, but had no effect on the growth of filamentous fungi or other types of fungi (Cryptococcus neoformans,Aspergillus fumigatus,Aspergillus flavus,Aspergillus niger,Fusarium moniliforme,Microsporum canis,Microsporum gypseum,Trichophyton rubrumandTrichophyton mentagrophytes), even at a concentration of 3.2 mM. CGA-N46 had an inhibitory effect on the proliferation of lung cancer A549 cells and a reversible effect on the growth of normal primary chicken embryo fibroblast cells, but no hemolytic activity on human erythrocytes at the minimum inhibitory concentration of CGA-N46 against yeasts. The antifungal activity of CGA-N46 was stable at a temperature <40°C or within a broad pH range (pH 5.0-7.0). Its antifungal activity was enhanced when the peptide was used in combination with fluconazole and terbinafine. The present results indicate that CGA-N46 is a safe, physicochemically stable, antifungal peptide with anticancer cell activity that exhibits an additive effect with conventional antibiotics.
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Li
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Lu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Lu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Hui-Ru
authors.initials: HR
authors.lastname: Zhang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Yin
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Sun
keywords: CGA-N46; Chromogranin A; additive combination; anti-proliferation; antifungal peptide; physicochemical stability