Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of Aphanomyces invadans, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model

Abstract

In this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, Aphanomyces invadans, have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical properties and the web-based predictions, which indicate that PS14 is non-toxic, and it has the potential to elicit anti-cancer and anti-inflammatory activities. These in silico results were experimentally validated through in vitro (L6 or Hep-2 cells) and in vivo (zebrafish embryo or larvae) models. Experimental results showed that PS14 is non-toxic in L6 cells and the zebrafish embryo, and it elicits an antitumor effect Hep-2 cells and zebrafish embryos. Anticancer activity assays, in terms of MTT, trypan blue and LDH assays, showed a dose-dependent inhibitory effect on cell proliferation. Moreover, in the epithelial cancer cells and zebrafish embryos, the peptide challenge (i) caused significant changes in the cytomorphology and induced apoptosis; (ii) triggered ROS generation; and (iii) showed a significant up-regulation of anti-cancer genes including BAX, Caspase 3, Caspase 9 and down-regulation of Bcl-2, in vitro. The anti-inflammatory activity of PS14 was observed in the cell-free in vitro assays for the inhibition of proteinase and lipoxygenase, and heat-induced hemolysis and hypotonicity-induced hemolysis. Together, this study has identified that PS14 has anti-cancer and anti-inflammatory activities, while being non-toxic, in vitro and in vivo. Future experiments can focus on the clinical or pharmacodynamics aspects of PS14.

Antioxidant Effects of Rutin Trihydrate vs. Doxorubicin in Zebrafish Larvae: GSH, GPx, and GST Activity

“…Our investigation primarily focused on assessing the levels of these crucial antioxidant enzymes. It is noteworthy that similar results, showing increased levels of antioxidant enzymes, have been reported following treatment with specific peptides designed to upregulate antioxidant defenses [9]. Conversely, we observed downregulation of GST, GPx, and GSH in zebrafish larvae exposed to H2O2, underlining the significant impact of the investigated treatments.…”

Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells

“…Following the data acquired for the four main complexes, a screening of their derivatives was performed adopting concentrations of 1, 5 and 20 μM and by using MTT assay, in order to compare their behavior with the main complexes [ 44 , 45 , 46 ]. All data are summarized in Figure 7 .…”

Aquatic Peptide: The Potential Anti-Cancer and Anti-Microbial Activity of GE18 Derived from Pathogenic Fungus Aphanomyces invadans

“…Zebrafish ( Danio rerio ) were commercially purchased from the NSK aquarium, Kolathur, Tamil Nadu, India. Fish were acclimatized to laboratory conditions; for breeding and the collection of embryos, a standard protocol was followed [ 18 , 19 , 20 , 21 ]. The 4 h post-fertilized (hpf) embryos were examined under the microscope.…”

“…The embryos, treated with hydrogen peroxide (1 mM, H 2 O 2 ), served as a positive control. The untreated was considered as the control, whereas the experimental group was treated with five peptide concentrations (10,20,30,40 or 50 µM). The treatment duration was 4 hpf to 96 hpf; parameters such as hatching rate, heart rate, survival rate, mortality rate and morphological abnormalities were analyzed.…”

“…The cytotoxicity of GE18 in MCF-7 cells was established through the LDH assay. Cells (5 × 10 4 /well) were treated with the peptide for 24 h at various concentrations (10,20,30,40 or 50 µM). Untreated cells served as the control, while the Triton-X-100-treated cells served as the positive control.…”