Ganoderma applanatum secondary metabolites induced apoptosis through different pathways: In vivo and in vitro anticancer studies

Biomed Pharmacother. 2018 May:101:264-277. doi: 10.1016/j.biopha.2018.02.058. Epub 2018 Feb 27.

Abstract

Ganoderma applanatum is a widely distributed saprobic or parasitic mushroom, it was found at the bases of decaying logs in Hakozaki Higashi-ku Fukuoka-shi. Japan. The mushroom was extracted with 80% methanol, and LC-HRMS analysis was conducted to illustrate the bioactive ingredients. The cytotoxicity of the total metabolite extract was evaluated against human colon cancer cell line (Caco-2) which showed IC50 value of 160 ± 4.08 μg/ml. G. applanatum methanolic extract caused different morphological alterations and increased glutathione level in the treated cells. Interestingly, G. applanatum increased Bax/Bcl-2 ratio significantly (P ˂ 0.05) at concentrations of 80 and 160 μg/ml on Caco-2 undergoing apoptotic p53-independent pathway with lake expression of p53 protein and up-regulated Cas-3 mRNA. The in vivo study on solid Ehrlich tumor (SEC) revealed a decrease in the volume of the developed tumor mass after five days of G. applanatum (200 μg/ml) treatment. The apoptotic p53-dependant pathway was confirmed by mRNA Bax/Bcl-2 increased ratio in addition to p53 and Cas-3 up-regulation. In conclusion, G. applanatum could exert apoptotic antitumor properties in Caco-2 by p53-independent pathway and p53-dependant in SEC. The findings proved that G. applanatum can be a promising candidate as alternative or co-anticancer medications.

Keywords: Anticancer; Apoptosis; Caco-2; Ganoderma applanatum; Mushroom; Solid Ehrlich tumor.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caco-2 Cells
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Chromatography, Liquid
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Female
  • Ganoderma / metabolism*
  • Glutathione / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Japan
  • Mass Spectrometry
  • Mice
  • Neoplasm Proteins
  • Secondary Metabolism
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • URGCP protein, human
  • Glutathione