Tumidulin, a Lichen Secondary Metabolite, Decreases the Stemness Potential of Colorectal Cancer Cells

Molecules. 2018 Nov 14;23(11):2968. doi: 10.3390/molecules23112968.

Abstract

Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness.

Keywords: colorectal cancer cells; lichen; oncogene; secondary metabolites; stemness potential; transcriptional regulation; tumidulin.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Biomarkers
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lichens / chemistry*
  • Molecular Structure
  • Neoplastic Stem Cells / drug effects*
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers
  • Plant Extracts