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1'-O-methyl-averantin isolated from the endolichenic fungus Jackrogersella sp. EL001672 suppresses colorectal cancer stemness via sonic Hedgehog and Notch signaling

Varlı, Mücahit ; Lee, Eun-Young ; Yang, Yi ; Zhou, Rui ; Taş, İsa LU orcid ; Pulat, Sultan ; Gamage, Chathurika D B ; Park, So-Yeon ; Hur, Jae-Seoun and Nam, Sang-Jip , et al. (2023) In Scientific Reports 13(1).
Abstract

Endolichenic fungi are host organisms that live on lichens and produce a wide variety of secondary metabolites. Colorectal cancer stem cells are capable of self-renewal and differentiation into cancer cells, which makes cancers difficult to eradicate. New alternative therapeutics are needed to inhibit the growth of tumor stem cells. This study examined the ability of an extract of Jackrogersella sp. EL001672 (derived from the lichen Cetraria sp.) and the isolated compound 1'-O-methyl-averantin to inhibit development of cancer stemness. The endolichenic fungus Jackrogersella sp. EL001672 (KACC 83021BP), derived from Cetraria sp., was grown in culture medium. The culture broth was extracted with acetone to obtain a crude extract. Column... (More)

Endolichenic fungi are host organisms that live on lichens and produce a wide variety of secondary metabolites. Colorectal cancer stem cells are capable of self-renewal and differentiation into cancer cells, which makes cancers difficult to eradicate. New alternative therapeutics are needed to inhibit the growth of tumor stem cells. This study examined the ability of an extract of Jackrogersella sp. EL001672 (derived from the lichen Cetraria sp.) and the isolated compound 1'-O-methyl-averantin to inhibit development of cancer stemness. The endolichenic fungus Jackrogersella sp. EL001672 (KACC 83021BP), derived from Cetraria sp., was grown in culture medium. The culture broth was extracted with acetone to obtain a crude extract. Column chromatography and reverse-phase HPLC were used to isolate an active compound. The anticancer activity of the extract and the isolated compound was evaluated by qRT-PCR and western blotting, and in cell viability, spheroid formation, and reporter assays. The acetone extract of EL001672 did not affect cell viability. However, 1'-O-methyl-averantin showed cytotoxic effects against cancer cell lines at 50 μg/mL and 25 μg/mL. Both the crude extract and 1'-O-methyl-averantin suppressed spheroid formation in CRC cell lines, and downregulated expression of stemness markers ALDH1, CD44, CD133, Lgr-5, Msi-1, and EphB1. To further characterize the mechanism underlying anti-stemness activity, we examined sonic Hedgehog and Notch signaling. The results showed that the crude extract and the 1'-O-methyl-averantin inhibited Gli1, Gli2, SMO, Bmi-1, Notch-1, Hes-1, and the CSL complex. Consequently, an acetone extract and 1'-O-methyl-averantin isolated from EL001672 suppresses colorectal cancer stemness by regulating the sonic Hedgehog and Notch signaling pathways.

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publishing date
type
Contribution to journal
publication status
published
keywords
Humans, Hedgehog Proteins/metabolism, Acetone/metabolism, Lichens/metabolism, Xylariales/metabolism, Colorectal Neoplasms/pathology, Neoplastic Stem Cells/metabolism, Cell Line, Tumor, Anthraquinones
in
Scientific Reports
volume
13
issue
1
article number
2811
publisher
Nature Publishing Group
external identifiers
  • scopus:85148258136
  • pmid:36797277
ISSN
2045-2322
DOI
10.1038/s41598-023-28773-z
language
English
LU publication?
no
additional info
© 2023. The Author(s).
id
ffe5e6c2-bec6-478d-81f0-0ebf930afa4a
date added to LUP
2026-09-23 15:58:35
date last changed
2026-10-09 03:01:12
@article{ffe5e6c2-bec6-478d-81f0-0ebf930afa4a,
  abstract     = {{<p>Endolichenic fungi are host organisms that live on lichens and produce a wide variety of secondary metabolites. Colorectal cancer stem cells are capable of self-renewal and differentiation into cancer cells, which makes cancers difficult to eradicate. New alternative therapeutics are needed to inhibit the growth of tumor stem cells. This study examined the ability of an extract of Jackrogersella sp. EL001672 (derived from the lichen Cetraria sp.) and the isolated compound 1'-O-methyl-averantin to inhibit development of cancer stemness. The endolichenic fungus Jackrogersella sp. EL001672 (KACC 83021BP), derived from Cetraria sp., was grown in culture medium. The culture broth was extracted with acetone to obtain a crude extract. Column chromatography and reverse-phase HPLC were used to isolate an active compound. The anticancer activity of the extract and the isolated compound was evaluated by qRT-PCR and western blotting, and in cell viability, spheroid formation, and reporter assays. The acetone extract of EL001672 did not affect cell viability. However, 1'-O-methyl-averantin showed cytotoxic effects against cancer cell lines at 50 μg/mL and 25 μg/mL. Both the crude extract and 1'-O-methyl-averantin suppressed spheroid formation in CRC cell lines, and downregulated expression of stemness markers ALDH1, CD44, CD133, Lgr-5, Msi-1, and EphB1. To further characterize the mechanism underlying anti-stemness activity, we examined sonic Hedgehog and Notch signaling. The results showed that the crude extract and the 1'-O-methyl-averantin inhibited Gli1, Gli2, SMO, Bmi-1, Notch-1, Hes-1, and the CSL complex. Consequently, an acetone extract and 1'-O-methyl-averantin isolated from EL001672 suppresses colorectal cancer stemness by regulating the sonic Hedgehog and Notch signaling pathways.</p>}},
  author       = {{Varlı, Mücahit and Lee, Eun-Young and Yang, Yi and Zhou, Rui and Taş, İsa and Pulat, Sultan and Gamage, Chathurika D B and Park, So-Yeon and Hur, Jae-Seoun and Nam, Sang-Jip and Kim, Hangun}},
  issn         = {{2045-2322}},
  keywords     = {{Humans; Hedgehog Proteins/metabolism; Acetone/metabolism; Lichens/metabolism; Xylariales/metabolism; Colorectal Neoplasms/pathology; Neoplastic Stem Cells/metabolism; Cell Line, Tumor; Anthraquinones}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{1'-O-methyl-averantin isolated from the endolichenic fungus Jackrogersella sp. EL001672 suppresses colorectal cancer stemness via sonic Hedgehog and Notch signaling}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-28773-z}},
  doi          = {{10.1038/s41598-023-28773-z}},
  volume       = {{13}},
  year         = {{2023}},
}