Antitumor potential of new low molecular weight antioxidative preparations from the white rot fungus Cerrena unicolor against human colon cancer cells

Anna Matuszewska,Marcin Grąz,Łukasz Matuszewski,Mateusz Pięt,Adrian Zając,Dawid Stefaniuk,Magdalena Jaszek,Roman Paduch,Renata Bancerz,Iga Cios

doi:10.1038/s41598-018-37947-z

Anna Matuszewska, Marcin Grąz + Show 8 more

Open Access

https://doi.org/10.1038/s41598-018-37947-z

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Abstract

The aim of this study was to investigate the anticancer and antioxidant activities of low molecular weight subfractions isolated from secondary metabolites produced by the wood degrading fungus Cerrena unicolor. Human colon cancer cells (stage I) HT-29 and human normal colon epithelial cells CCD 841 CoTr were used in the research. The present study demonstrated that the low molecular weight subfractions exhibited inhibitory activity towards human colon cancer cells HT-29 at a concentration range of 25–200 μg/mL. All 6 subfractions inhibited proliferation of cells down to 47.5–9.2% at the highest concentrations in a dose-dependent manner. The most desired activity was exhibited by subfractions S, 3, 4, and 5, as the proliferation of HT-29 cells was inhibited to the greatest extent (16.5, 47.5, 42.7, and 26.1% of the control, respectively), while the effect on CCD 841 CoTr cells was the mildest (inhibition to 54.4, 71.4, 79.4, and 53.4%, compared to the control, respectively). The microscopic observation revealed that all extracts induced programmed cell death, i.e. apoptosis (up to 44.4% (subfraction 6) towards HT-29 and less than 20% (most fractions) towards CCD 841 CoTr), with no or a significantly low level of necrosis in both cell lines at the same time.

Highlights

Mushrooms offer a wide range of benefits associated with consumption thereof and, they are regarded as functional foods[1]
Bisabolol produced by Inonotus rickii inhibits the development of myeloid leukemia as well as breast, colorectal, lung, and liver cancers[13], and sesquiterpenoids isolated from Pleurotus cornucopiae are characterized by cytotoxicity to cervical cancer cells (HeLa) and liver cancer cells[14]
Our previous studies demonstrated that the extracellular fraction of secondary metabolites of less than 10 kDa had cytotoxic, antioxidant, and antimicrobial effects; further fractionation was performed in order to examine the individual subfractions[22,23,24,25]

Summary

Introduction

Mushrooms offer a wide range of benefits associated with consumption thereof and, they are regarded as functional foods[1]. The bioactive substances produced by fungi can be divided into two main groups: low molecular compounds, e.g. terpenoids or phenolic compounds, and high molecular weight compounds, e.g. polysaccharides and enzymes[3]. Both groups of compounds exhibit biological activities such as antioxidant, anticancer, immunostimulating, antiatherosclerotic, neuroprotective, anti-inflammatory, antiallergic, antibacterial, antiviral, or hypoglycemic effects. Bisabolol produced by Inonotus rickii inhibits the development of myeloid leukemia as well as breast, colorectal, lung, and liver cancers[13], and sesquiterpenoids isolated from Pleurotus cornucopiae are characterized by cytotoxicity to cervical cancer cells (HeLa) and liver cancer cells[14] Phenols are another important group of low-molecular compounds of fungal origin. From the point of view of possible biomedical applications, it was important to characterize and separate the preparation obtained from the culture fluid of C. unicolor, which was used for determination of its qualitative composition as well as biological properties (especially the anticancer effect)

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