Ganoderma Lucidum induces oxidative DNA damage and enhances the effect of 5-Fluorouracil in colorectal cancer in vitro and in vivo
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31561886
DOI
10.1016/j.mrgentox.2019.06.001
PII: S1383-5718(19)30094-4
Knihovny.cz E-resources
- Keywords
- 5-Fluorouracil, Colorectal cancer, Combination therapy, DNA damage, Ganoderma Lucidum,
- MeSH
- Adenocarcinoma drug therapy pathology MeSH
- Antimetabolites, Antineoplastic pharmacology therapeutic use MeSH
- Cell Division drug effects MeSH
- DNA, Neoplasm drug effects MeSH
- Fluorouracil pharmacology therapeutic use MeSH
- Neoplasm Invasiveness MeSH
- Colorectal Neoplasms drug therapy pathology MeSH
- Comet Assay MeSH
- Drug Screening Assays, Antitumor MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Oxidative Stress MeSH
- DNA Damage * MeSH
- Reactive Oxygen Species metabolism MeSH
- Reishi chemistry MeSH
- Plant Extracts isolation & purification pharmacology MeSH
- Drug Synergism MeSH
- Tumor Stem Cell Assay MeSH
- Tumor Burden drug effects MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antimetabolites, Antineoplastic MeSH
- DNA, Neoplasm MeSH
- Fluorouracil MeSH
- Reactive Oxygen Species MeSH
- Plant Extracts MeSH
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.
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