Grifola frondosa polysaccharides induce breast cancer cell apoptosis via the mitochondrial-dependent apoptotic pathway

Int J Mol Med. 2017 Oct;40(4):1089-1095. doi: 10.3892/ijmm.2017.3081. Epub 2017 Jul 26.

Abstract

Grifola frondosa, a type of food and medical fungus, has been shown to exhibit various pharmacological activities, including anticancer effects. As the most typical cancer diagnosed among female patients, breast cancer remains a huge concern threatening human health globally. In the present study, the anti-breast cancer effects of Grifola frondosa polysaccharides (GFPs) and the underlying mechanisms were investigated in MCF-7 and MDA-MB-231 cells, as well as in nude mice bearing MCF-7 tumor xenografts. GFPs exerted cytotoxic effects on the cells, as indicated by a decrease in cell viability, and an increase in the apoptototic rate, lactate dehydrogenase release and reactive oxygen species accumulation, inducing mitochondrial dysfunction. The increased expression of Bax, cleaved caspase-3 and caspase-8, and the reduced levels of B-cell lymphoma 2 (Bcl-2) and Bcl-extra large (Bcl‑xL) were observed in the cells incubated with GFPs and in the tumor tissues of the mice treated with GFPs. Moreover, the GFPs significantly suppressed the phosphorylation of AKT/glycogen synthase kinase-3β and extracellular signal-regulated kinases in a time-dependent manner. Finally, the inhibition of MCF-7 tumor xenograft growth further confirmed the anti-breast cancer effects of GFPs. All these findings revealed that GFPs induced human breast cancer cell apoptosis via the mitochondrial-dependent apoptotic pathway, and provide experimental evidence to support the use of Grifola frondosa as a potential treatment for breast cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Female
  • Fungal Polysaccharides / isolation & purification
  • Fungal Polysaccharides / pharmacology*
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Grifola / chemistry*
  • Humans
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2 protein, human
  • BCL2L1 protein, human
  • Fungal Polysaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8