Ganoderma Lucidum induces oxidative DNA damage and enhances the effect of 5-Fluorouracil in colorectal cancer in vitro and in vivo.
Adenocarcinoma
/ drug therapy
Animals
Antimetabolites, Antineoplastic
/ pharmacology
Cell Division
/ drug effects
Cell Line, Tumor
Colorectal Neoplasms
/ drug therapy
Comet Assay
DNA Damage
DNA, Neoplasm
/ drug effects
Drug Screening Assays, Antitumor
Drug Synergism
Female
Fluorouracil
/ pharmacology
Mice
Mice, Inbred BALB C
Neoplasm Invasiveness
Oxidative Stress
Plant Extracts
/ isolation & purification
Reactive Oxygen Species
/ metabolism
Reishi
/ chemistry
Tumor Burden
/ drug effects
Tumor Stem Cell Assay
5-Fluorouracil
Colorectal cancer
Combination therapy
DNA damage
Ganoderma Lucidum
Journal
Mutation research. Genetic toxicology and environmental mutagenesis
ISSN: 1879-3592
Titre abrégé: Mutat Res Genet Toxicol Environ Mutagen
Pays: Netherlands
ID NLM: 101632149
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
22
03
2019
revised:
31
05
2019
accepted:
01
06
2019
entrez:
29
9
2019
pubmed:
29
9
2019
medline:
24
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31561886
pii: S1383-5718(19)30094-4
doi: 10.1016/j.mrgentox.2019.06.001
pii:
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
DNA, Neoplasm
0
Plant Extracts
0
Reactive Oxygen Species
0
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
403065Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.