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

Yang, Yi ; Bhosle, Suresh R ; Yu, Young Hyun ; Park, So-Yeon ; Zhou, Rui ; Taş, İsa LU ; Gamage, Chathurika D B ; Kim, Kyung Keun ; Pereira, Iris and Hur, Jae-Seoun , et al. (2018) In Molecules (Basel, Switzerland) 23(11). p.1-13
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Antineoplastic Agents, Phytogenic/chemistry, Biomarkers, Cell Line, Tumor, Colorectal Neoplasms/genetics, Gene Expression Regulation, Neoplastic/drug effects, Humans, Lichens/chemistry, Molecular Structure, Neoplastic Stem Cells/drug effects, Plant Extracts/chemistry, Signal Transduction/drug effects, Tumor Cells, Cultured
in
Molecules (Basel, Switzerland)
volume
23
issue
11
article number
2968
pages
1 - 13
publisher
MDPI AG
external identifiers
  • scopus:85056537349
  • pmid:30441806
ISSN
1420-3049
DOI
10.3390/molecules23112968
language
English
LU publication?
no
id
5271fb7e-9563-4cdb-805f-c7feb5a56abf
date added to LUP
2022-08-25 14:39:59
date last changed
2024-03-20 13:38:35
@article{5271fb7e-9563-4cdb-805f-c7feb5a56abf,
  abstract     = {{<p>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.</p>}},
  author       = {{Yang, Yi and Bhosle, Suresh R and Yu, Young Hyun and Park, So-Yeon and Zhou, Rui and Taş, İsa and Gamage, Chathurika D B and Kim, Kyung Keun and Pereira, Iris and Hur, Jae-Seoun and Ha, Hyung-Ho and Kim, Hangun}},
  issn         = {{1420-3049}},
  keywords     = {{Antineoplastic Agents, Phytogenic/chemistry; Biomarkers; Cell Line, Tumor; Colorectal Neoplasms/genetics; Gene Expression Regulation, Neoplastic/drug effects; Humans; Lichens/chemistry; Molecular Structure; Neoplastic Stem Cells/drug effects; Plant Extracts/chemistry; Signal Transduction/drug effects; Tumor Cells, Cultured}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  pages        = {{1--13}},
  publisher    = {{MDPI AG}},
  series       = {{Molecules (Basel, Switzerland)}},
  title        = {{Tumidulin, a Lichen Secondary Metabolite, Decreases the Stemness Potential of Colorectal Cancer Cells}},
  url          = {{http://dx.doi.org/10.3390/molecules23112968}},
  doi          = {{10.3390/molecules23112968}},
  volume       = {{23}},
  year         = {{2018}},
}