Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A

Abstract

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 tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. 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 f umigatus, Aspergillus f lavus, Aspergillus niger, Fusarium moniliforme, Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton 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.

The Antifungal Peptide MCh-AMP1 Derived From Matricaria chamomilla Inhibits Candida albicans Growth via Inducing ROS Generation and Altering Fungal Cell Membrane Permeability

“…Minimum inhibitory concentrations (MIC) for the peptide has been measured as described previously (Li et al, 2015;Seyedjavadi et al, 2019). Briefly, fungal cells, diluted to 5 × 10 5 cells/mL in Sabouraud dextrose broth medium, incubated with several concentrations of the peptide at 35 • C for 24 h. The MIC was taken as the lowest concentration that will prevent the growth of the fungal cells.…”

Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei

“…To further explore the antifungal activity of the vasostatin-1 derived peptide and avoid aggregation, CGA-N46 which corresponded to human CGA residues 31-76 was synthesized. Our previous studies elucidated that CGA-N46 peptide had specific anti-Candidal activity, especially showed the highest antagonistic activity to C. krusei, without hemolytic activity on human erythrocytes in vitro (20). CGA-N46 inhibited the growth of Candida species by decreasing intracellular reactive oxygen species levels and mitochondria membrane potentials while also inhibiting DNA synthesis (21).…”

The antifungal peptide CGA-N12 inhibits cell wall synthesis of Candida tropicalis by interacting with KRE9

“…The primers for PCR used in this study are listed in Table 3. The AMP CGA-N12 with N-terminal and C-terminal deprotection was synthesized by performing solid-phase synthesis according to a previously reported method [28]. Other chemicals used in the present study were of analytical grade and from commercial suppliers.…”

“…Those CGA-derived peptides, particularly in the N-terminal domain, exhibit antibacterial and antifungal activity [27]. CGA-N12corresponding to the region from the 65th to 76th amino acid of the N terminus of CGA has been shown to have specific anti-Candida activity with less haemolytic activity [28] and therapeutic effects in infected animal models [29]. CGA-N12 induces an overgeneration of intracellular reactive oxygen species and a dissipation of mitochondrial membrane potential.…”