Possibility to Biotransform Anthracyclines by Peroxidases Produced by Bjerkandera adusta CCBAS 930 with Reduction of Geno- and Cytotoxicity and Pro-Oxidative Activity.

Kamila Rybczyńska-Tkaczyk,Teresa Korniłłowicz-Kowalska,Konrad A Szychowski

doi:10.3390/molecules26020462

Abstract

The aim of this study was to evaluate the bioremoval mechanism of anthracycline antibiotics by the white-rot fungus B. adusta CCBAS 930. The activity of oxidoreductases and levels of phenolic compounds and free radicals were determined during the biotransformation of anthraquinone antibiotics: daunomycin (DNR) and doxorubicin (DOX) by B. adusta strain CCBAS 930. Moreover, phytotoxicity (Lepidium sativum L.), ecotoxicity (Vibrio fischeri), genotoxicity and cytotoxicity of anthraquinone dyes were evaluated before and after biological treatment. More than 80% and 90% of DNR and DOX were removed by biodegradation (decolorization). Initial solutions of DNR and DOX were characterized by eco-, phyto-, geno- and cytotoxicity. Despite efficient decolorization, secondary metabolites, toxic to bacteria, formed during biotransformation of anthracycline antibiotics in B. adusta CCBAS 930 cultures. DNR and DOX metabolites did not increase reactive oxygen species (ROS) production in human fibroblasts and resazurin reduction. DNR metabolites did not change caspase-3 activity.

Highlights

The development of civilization and accelerated pace of life have led to a global increase in the incidence of cancer in the last decade [1]
In 20-day-old cultures, B. adusta strain CCBAS 930 removed more than 90% of AQAs
We suggested that high biotoxicity level after anthracycline treatments with B. adusta CCBAS 930 was probably connected with a high concentration of phenolic compounds

Summary

Introduction

The development of civilization and accelerated pace of life have led to a global increase in the incidence of cancer in the last decade [1]. The increase in the survival age average has increased the occurrence of cancer. This resulted in a more than two-fold increase in the production of anti-tumor drugs [2]. One of the main groups of drugs used to treat cancer are DNA intercalators (cytostatic drugs), which include anthracycline antibiotics (AQA), mainly daunomycin (DNR) and doxorubicin (DOX) [3]. Daunomycin (DNR), known as daunorubicin, is a chemotherapeutic used to treat cancer, especially acute myeloid and lymphocytic leukemias, chronic myelogenous leukemia and Kaposi’s sarcoma. China and India (50%), the United States (28%), Europe (15%) and Japan (12%) are the main producers of cytostatic drugs [3]

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