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2,3,5-Trimethoxy-4-cresol, an anti-metastatic constituent from the solid-state cultured mycelium of Antrodia cinnamomea and its mechanism

Abstract

Antrodia cinnamomea is a valuable and unique edible fungus originating from the forests of Taiwan. In this study, an anti-metastatic compound, 2,3,5-trimethoxy-4-cresol (TMC), was isolated from the solid-state cultured mycelium of A. cinnamomea. According to the results obtained from cell wound healing, cell migration and invasion assays, TMC effectively suppressed movement, migration and invasion of lung cancer cells at the dosage of 5–40 μM, which was non-toxic to A549 cells. In addition, TMC reduced protein expression of Akt, MMP-2 and MMP-9 and enhanced E-cadherin and TIMP-1 protein expression, which are known to regulate cell adhesion, migration and invasion. Taken together, TMC effectively suppresses movement, migration and invasion of lung cancer cells, and achieves an anti-cancer metastasis effect.

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Abbreviations

DMSO:

Dimethyl sulfoxide

DPBS:

Dulbecco’s phosphate-buffered saline

ECM:

Extracellular matrix

EMT:

Epithelial–mesenchymal transition

FAK:

Focal adhesion kinase

FBS:

Fetal bovine serum

GA:

Gallic acid

MMP:

Matrix metalloproteinase

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide

NSCLC:

Non-small-cell lung cancer

SDS:

Sodium dodecyl sulfate

TEMED:

N,N,N’,N’-Tetra-methylethylenediamine

TIMP-2:

Tissue inhibitor of metalloproteinase-2

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

Parts of this study were supported by the Ministry of Science and Technology, Taiwan, Republic of China (NSC-103-2911-I-005-301, NSC-102-2911-I-005-301) and the Ministry of Education, Taiwan, R.O.C. under the ATU plan.

Conflict of interest

No competing financial interests exist.

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Correspondence to Jong-Tar Kuo or Sheng-Yang Wang.

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Lin, CC., Chen, CC., Kuo, YH. et al. 2,3,5-Trimethoxy-4-cresol, an anti-metastatic constituent from the solid-state cultured mycelium of Antrodia cinnamomea and its mechanism. J Nat Med 69, 513–521 (2015). https://doi.org/10.1007/s11418-015-0916-6

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  • DOI: https://doi.org/10.1007/s11418-015-0916-6

Keywords

  • Antrodia cinnamomea
  • 2,3,5-Trimethoxy-4-cresol
  • Anti-metastasis
  • EMT