Fungus Cerrena unicolor as an effective source of new antiviral, immunomodulatory, and anticancer compounds

Int J Biol Macromol. 2015 Aug:79:459-68. doi: 10.1016/j.ijbiomac.2015.05.015. Epub 2015 May 21.

Abstract

In the report, three bioactive fractions from Cerrena unicolor: laccase (LAC), endopolysaccharides (c-EPL), and low molecular weight (ex-LMS) were tested for the first time towards their antiviral, immunostimulatory, cytotoxic and antiproliferative effect. The immunomodulatory activity was studied by means of THP-1-derived macrophages able to synthesize and secrete IL-6 and TNF-α. We used cervical carcinoma cell lines SiHa (ATCC, HTB-35) and CaSki (ATCC, CRL 1550) to determine antitumor activity and human skin fibroblasts (HSF) as a control. SiHa and L929 cell lines were used in the antiviral activity assay to propagate HHV-1 and EMCV, respectively. LAC was the most active against HSV at an early stage of viral replication, whereas the activity of laccase against EMCV was evident after incubation of the virus with LAC before and after the adsorption step. Moreover, the investigations showed that the fungal c-EPL fraction stimulated the production and secretion of TNF-α and IL-6 by THP-1-derived macrophages up to a level of 2000 pg/ml and 400 pg/ml, respectively. It was indicated for the first time that the LAC and ex-LMS fractions exhibited anticancer activity. This resulted from their cytotoxic or antiproliferative action against the investigated tumor cells at concentrations above 250 μg/ml and 10 μg/ml, respectively.

Keywords: Antiviral and anticancer activity; Endopolysaccharides; Immunostimulation; Laccase; Low molecular weight compounds; White rot fungi.

MeSH terms

  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / isolation & purification*
  • Antiviral Agents / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Encephalomyocarditis virus / drug effects
  • Encephalomyocarditis virus / physiology
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Fibroblasts / virology
  • Fungal Polysaccharides / isolation & purification*
  • Fungal Polysaccharides / pharmacology
  • Fungal Proteins / isolation & purification*
  • Fungal Proteins / pharmacology
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / physiology
  • Humans
  • Immunologic Factors / isolation & purification*
  • Immunologic Factors / pharmacology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / metabolism
  • Laccase / isolation & purification*
  • Laccase / pharmacology
  • Macrophages / drug effects
  • Macrophages / pathology
  • Macrophages / virology
  • Polyporaceae / chemistry*
  • Polyporaceae / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism
  • Virus Replication / drug effects

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Fungal Polysaccharides
  • Fungal Proteins
  • IL6 protein, human
  • Immunologic Factors
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Laccase