Thromboelastometric Analysis of Anticancer Cerrena unicolor Subfractions Reveal Their Potential as Fibrin Glue Drug Carrier Enhancers

Biomolecules. 2021 Aug 24;11(9):1263. doi: 10.3390/biom11091263.

Abstract

In this study, the influence of two subfractions (with previously proven anti-cancer properties) isolated from wood rot fungus Cerrena unicolor on the formation of a fibrin clot was investigated in the context of potential use as fibrin glue and sealant enhancers and potential wound healing agents. With the use of ROTEM thromboelastometry, we demonstrated that, in the presence of fibrinogen and thrombin, the S6 fraction accelerated the formation of a fibrin clot, had a positive effect on its elasticity modulus, and enhanced the degree of fibrin cross-linking. The S5 fraction alone showed no influence on the fibrin coagulation process; however, in the presence of fibrin, it exhibited a decrease in anti-proliferative properties against the HT-29 line, while it increased the proliferation of cells in general at a concentration of 100 µg/mL. Both fractions retained their proapoptotic properties to a lesser degree. In combination with the S6 fraction in the ratio of 1:1 and 1:3, the fractions contributed to increased inhibition of the activity of matrix metalloproteinases (MMPs). This may suggest anti-metastatic activity of the combined fractions. In conclusion, the potential of the fractions isolated from the C. unicolor secretome to be used as a means of improving the wound healing process was presented. The potential for delivering agents with cytostatic properties introduced far from the site of action or exerting a pro-proliferative effect at the wound site with the aid of a fibrin sealant was demonstrated.

Keywords: CCD 841 CoTr; Cerrena unicolor; HT-29; fibrin coagulation; fibrin-based sealant; low molecular weight subfractions.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blood Coagulation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Carriers / chemistry*
  • Elasticity
  • Fibrin / metabolism
  • Fibrin Tissue Adhesive / pharmacology*
  • Fungi / drug effects
  • Gelatin / metabolism
  • Humans
  • Kinetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Polyporales / chemistry*
  • Thrombelastography*
  • Thrombin / pharmacology
  • Viscosity

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Fibrin Tissue Adhesive
  • Gelatin
  • Fibrin
  • Thrombin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9

Supplementary concepts

  • Cerrena unicolor