Ganoderma Lucidum induces oxidative DNA damage and enhances the effect of 5-Fluorouracil in colorectal cancer in vitro and in vivo

. 2019 Sep ; 845 () : 403065. [epub] 20190603

Jazyk angličtina Země Nizozemsko Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid31561886
Odkazy

PubMed 31561886
DOI 10.1016/j.mrgentox.2019.06.001
PII: S1383-5718(19)30094-4
Knihovny.cz E-zdroje

The first-line chemotherapy of colorectal cancer (CRC), besides surgery, comprises administration of 5-Fluorouracil (5FU). Apart from cytotoxic effect on cancer cells, 5FU may also cause adverse side effects. Ganoderma Lucidum (GLC) is a mushroom used in Traditional Eastern Medicine. We propose that natural compounds, particularly GLC extracts, may sensitize cancer cells to conventional chemotherapeutics. This combination therapy could lead to more selective cancer cell death and may improve the response to the therapy and diminish the adverse effects of anticancer drugs. Here we demonstrate that GLC induced oxidative DNA damage selectively in colorectal cancer cell lines, whereas it protected non-malignant cells from the accumulation of reactive oxygen species. Accumulation of DNA damage caused sensitization of cancer cells to 5FU resulting in improved anticancer effect of 5FU. The results obtained in colorectal cell lines were confirmed in in vivo study: GLC co-treatment with 5FU increased the survival of treated mice and reduced the tumor volume in comparison with group treated with 5FU alone. Combination of conventional chemotherapeutics and natural compounds is a promising approach, which may reduce the effective curative dose of anticancer drugs, suppress their adverse effects and ultimately lead to better quality of life of CRC patients.

Biomedical centre of Academy of Sciences of Slovak Republic Dubravska cesta 9 845 05 Bratislava Slovak Republic

Department of Hepatology and Gastroenterology Institute for Clinical and Experimental Medicine Videnska 1958 9 140 21 Prague Czech Republic

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic; Department of Medical Genetics 3rd Faculty of Medicine Charles University Ruska 87 100 00 Prague Czech Republic

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic; DSTest Laboratories Purdue Research Park 5225 Exploration Drive IN 46241 Indianapolis IN United States

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic; Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Albertov 4 128 00 Prague Czech Republic

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic; Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Albertov 4 128 00 Prague Czech Republic; Biomedical Centre Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 76 323 00 Pilsen Czech Republic

Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic; Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Albertov 4 128 00 Prague Czech Republic; Department of Medical Genetics 3rd Faculty of Medicine Charles University Ruska 87 100 00 Prague Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

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