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

Mutat Res Genet Toxicol Environ Mutagen. 2019 Sep:845:403065. doi: 10.1016/j.mrgentox.2019.06.001. Epub 2019 Jun 3.

Abstract

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.

Keywords: 5-Fluorouracil; Colorectal cancer; Combination therapy; DNA damage; Ganoderma Lucidum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Comet Assay
  • DNA Damage*
  • DNA, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Oxidative Stress
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Reishi / chemistry*
  • Tumor Burden / drug effects
  • Tumor Stem Cell Assay

Substances

  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • Plant Extracts
  • Reactive Oxygen Species
  • Fluorouracil