Coriolus versicolor and its bioactive molecule are potential immunomodulators against cancer cell metastasis via inactivation of MAPK pathway

J Ethnopharmacol. 2023 Jan 30:301:115790. doi: 10.1016/j.jep.2022.115790. Epub 2022 Oct 5.


Ethnopharmacological relevance: Coriolus versicolor (CV) has been used in traditional Chinese medicine for over 2000 years as a premium medicine for enhancing good health and longevity. The immunomodulatory and anti-cancer effects of polysaccharopeptides (PSP) from cultured CV have been extensively studied; however, the effect and the mechanism of action of other small molecules from CV remain unknown.

Aim of the study: we aim to examine the immunomodulatory and anti-cancer effects of the small molecules from CV (SMCV) and identify the active compounds that are responsible for the biological effects against glioblastoma multiforme cells.

Materials and methods: The effects of SMCV/active compound on cytokine and MMP mRNA expressions and productions were assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. An active compound from SMCV was identified with a bioassay-guided fractionation scheme. The potential mode of action of the active compound was further investigated by identifying the cell signaling pathway. The protein expressions of phospho-ERK, phospho-JNK and phospho-p38 MAPKs were measured by Western Blotting. The anti-invasive effect of SMCV/bioactive compound against T98G, lung carcinoma (A549), and breast adenocarcinoma (MDA-MB-231) cells were determined using invasion assay.

Results: Our results showed that SMCV had strong immunomodulatory effect by suppressing LPS-induced TNF-α production, whereas increasing poly I:C-induced IFN-β level in PBMac. SMCV not only possessed indirect anti-cancer effect by suppressing TNF-α-induced MMP-3 production in glioblastoma T98G cells, but also directly reduced the invasion ability of malignant cells including T98G, A549 and MDA-MB-231. Using bioassay-guided fractionation scheme, we isolated 9-KODE methyl ester (compound AM) that was responsible for the bioactivity of SMCV. This compound suppressed TNF-α-induced MMP-3 production in T98G cells and the suppression may be correlated with the inactivation of p38 mitogen-activated protein kinase (MAPK) pathway. Moreover, compound AM also directly reduced T98G cell invasion.

Conclusion: Results of our present study provides scientific evidence that SMCV possesses immunomodulatory and anti-cancer effects. Its bioactive compound, compound AM, is a potential new drug candidate against the invasion and metastasis of glioblastoma cells.

Keywords: 9-KODE methyl Ester; Anti-Invasion; Coriolus versicolor; Glioblastoma; Immunomodulatory.

MeSH terms

  • Glioblastoma* / drug therapy
  • Humans
  • Immunologic Factors / pharmacology
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 3
  • Mitogen-Activated Protein Kinases* / metabolism
  • Neoplasm Metastasis
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases


  • Immunologic Factors
  • Matrix Metalloproteinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Tumor Necrosis Factor-alpha

Supplementary concepts

  • Trametes versicolor