Extracts of Cordyceps sinensis inhibit breast cancer cell metastasis via down-regulation of metastasis-related cytokines expression

J Ethnopharmacol. 2018 Mar 25;214:106-112. doi: 10.1016/j.jep.2017.12.012. Epub 2017 Dec 15.

Abstract

Ethnopharmacological relevance: Cordyceps sinensis is a traditional Chinese medicine and has been used as adjuvant treatments for cancer and it has been also demonstrated to be effective in cancer patients.

Aim of the study: The objective of the present study is to investigate the anti-metastasis effects of water extracts of Cordyceps sinensis (WECS) in breast cancer and the potential mechanisms.

Materials and methods: The cytotoxicity of WECS on 4T1 breast cancer cells was evaluated in vitro using cell counting kit-8 (CCK8) assay. The in vivo anti-metastatic activity of intraperitoneally administered WECS and its effect on animal survival were measured in a mouse breast cancer metastasis model. To explore the molecular mechanisms of the anti-metastasis effect of WECS, the expression of matrix metalloprotein-9 (MMP-9) in serum was determined by enzyme-linked immunosorbent assay (ELISA). In addition, a protein array was used to examine the cytokine expression profiles in lung homogenates.

Results: Treatment with WECS (0.10-0.40mg/ml) significantly inhibited 4T1 cell viability in vitro. In animal studies, 50mg/kg WECS significantly reduced the number of metastatic lung nodules and the weight of lung, without affecting body weight of mice. Furthermore, WECS increased the survival rate of 4T1 tumor bearing mice in a dose dependent manner, and at high dose, WECS (50mg/kg) significantly increased the life span of the mice compared to untreated control group. The expression level of MMP-9 in serum was decreased about 50% in 50mg/kg WECS treated group compared to control group. The results of protein array showed that the expression of CC chemokine ligand 17 (CCL17), MMP-9, osteopontin (OPN), interleukin-33 (IL-33), CC chemokine ligand 12 (CCL12) and CC chemokine ligand 6 (CCL6) in the lungs of 4T1 tumor bearing mice was increased more than two fold compared with normal mice. Among them, the expression of CCL17, MMP-9, OPN, IL-33 was significantly reduced by treatment of 50mg/kg WECS.

Conclusion: Our results demonstrated that WECS has potent anti-metastasis activity in a mouse breast cancer metastasis model possibly by down-regulation the expression of several metastasis-related cytokines.

Keywords: Breast cancer; Cordyceps sinensis; Cytokines; Metastasis.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cordyceps / chemistry
  • Cytokines / genetics
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Osteopontin / metabolism
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal

Substances

  • Antineoplastic Agents, Phytogenic
  • Cytokines
  • Plant Extracts
  • Spp1 protein, mouse
  • Osteopontin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse