Medicinal mushrooms have been used for centuries against cancer and infectious diseases. These positive biological effects of mushrooms are due in part to the indirect action of stimulating immune cells. The objective of the current study is to investigate the possible immunomodulatory effects of mushroom polysaccharides on NK cells against different cancer cells. In this current study, fruiting bodies isolated from cultured Pleurotus ostreatus were extracted and partially purified using DEAE ion-exchange chromatography. The activation action of the collected fractions on Natural Killer cells was quantified against three different cancer cell lines in the presence or absence of human recombinant IL2 using three different activation and co-culture conditions. The possible modes of action of mushroom polysaccharides against cancer cells were evaluated at the cellular and molecular levels. Our results indicate that P. ostreatus polysaccharides induced NK-cells cytotoxic effects against lung and breast cancer cells with the largest effect being against breast cancer cells (81.2%). NK cells activation for cytokine secretion was associated with upregulation of KIR2DL genes while the cytotoxic activation effect of NK cells against cancer cells correlated with NKG2D upregulation and induction of IFNγ and NO production. These cytotoxic effects were enhanced in the presence of IL2. Analysis of the most active partially purified fraction indicates that it is predominantly composed of glucans. These results indicate bioactive 6-linked glucans present in P. ostreatus extracts activate NK-cell cytotoxicity via regulation of activation and induction of IFNγ and NO. These studies establish a positive role for bioactive P. ostreatus polysaccharides in NK-cells activation and induction of an innate immune response against breast and lung cancer cells.
Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain Pseudomonas PA1201. Both phz1 and phz2 gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between oxyR expression and PCA biosynthesis. Deletion of oxyR and overexpression of oxyR both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in phz1 and phz2. Overexpression of oxyR activated the expression of phz1 and phz1-dependent PCA production. However, overexpression of oxyR had little effect on phz2-dependent PCA biosynthesis, while deletion of oxyR promoted phz2-dependent PCA production and exerted a negative effect on phz2 expression. Further, OxyR directly bound to the phz2 promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated pqs QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA phrS plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the phrS promoter region to positively regulate phrS expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
Streptomycetes have been the center of attraction within scientific community owing to their capability to produce various bioactive compounds, for instance, with different antimicrobial, anticancer, and antioxidant properties. The search for novel Streptomyces spp. from underexplored area such as mangrove environment has been gaining attention since these microorganisms could produce pharmaceutically important metabolites. The aim of this study is to discover the diversity of Streptomyces spp. from mangrove in Sarawak and their bioactive potentials - in relation to antioxidant and cytotoxic activities. A total of 88 Streptomyces isolates were successfully recovered from the mangrove soil in Kuching, state of Sarawak, Malaysia. Phylogenetic analysis of all the isolates and their closely related type strains using 16S rRNA gene sequences resulted in 7 major clades in the phylogenetic tree reconstructed based on neighbour-joining algorithm. Of the 88 isolates, 18 isolates could be considered as potentially novel species according to the 16S rRNA gene sequence and phylogenetic analyses. Preliminary bioactivity screening conducted on the potential novel Streptomyces isolates revealed significant antioxidant activity and notable cytotoxic effect against tested colon cancer cell lines (HCT-116, HT-29, Caco-2, and SW480), with greater cytotoxicity towards SW480 and HT-29 cells. This study highlighted that the Sarawak mangrove environment is a rich reservoir containing streptomycetes that could produce novel secondary metabolites with antioxidant and cytotoxic activities.
Epinecidin-1 is an antimicrobial peptide derived from the orange-spotted grouper (Epinephelus coioides). The mature epinecidin-1 peptide is predicted to have an amphipathic α-helical structure and a non-helical hydrophilic domain at the C-terminal RRRH. The majority of work studying the potential pharmacological activities of epinecidin-1, utilize synthesized epinecidin-1 (Epi-1), which is made up of 21 amino acids, from the amino acid sequence of 22-42 residues of Epi-1-GFIFHIIKGLFHAGKMIHGLV. The synthetized Epi-1 peptide has been demonstrated to possess diverse pharmacological activities, including antimicrobial, immunomodulatory, anticancer, and wound healing properties. It has also been utilized in different clinical and agricultural fields, including topical applications in wound healing therapy as well as the enhancement of fish immunity in aquaculture. Hence, the present work aims to consolidate the current knowledge and findings on the characteristics and pharmacological properties of epinecidin-1 and its potential applications.