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. 2025 Nov 15.
doi: 10.1002/ptr.70126. Online ahead of print.

Atranorin Impedes Glioma Invasiveness and Progression by Inhibiting the Epithelial-Mesenchymal Transition and Stemness in Monotherapy and in Combination Therapy With Temozolomide

Rui Zhou  1 , Eun-Jung Ahn  2 , Suresh R Bhosle  1 , Ju Yeon Yu  1 , Yi Yang  1 , So-Yeon Park  1 , İsa Taş  1   3 , Chathurika Gamage  1 , Sultan Pulat  1 , Mücahit Varlı  1 , Jae-Seoun Hur  3 , Kyung Keun Kim  4 , Kyung-Hwa Lee  5 , Hyung-Ho Ha  1 , Sang Kyum Kim  6 , Kyung-Sub Moon  2 , Hangun Kim  1
Affiliations

Atranorin Impedes Glioma Invasiveness and Progression by Inhibiting the Epithelial-Mesenchymal Transition and Stemness in Monotherapy and in Combination Therapy With Temozolomide

Rui Zhou et al. Phytother Res. .

Abstract

Lichens are commensal organisms that contain secondary metabolites such as atranorin, which have intrinsic bioactive properties, including anticancer effects. The present study aimed to investigate the therapeutic potential and molecular mechanisms of atranorin and its hydrolytic derivatives in monotherapy and in combination treatment with temozolomide in glioma. The effects of atranorin on gliomas were investigated using an MTT assay, transwell invasion assay, spheroid formation assay, clonogenic assay, reporter assay, western blotting, quantitative real-time PCR, an orthotopic mouse glioma model with in vivo bioluminescence imaging, and immunohistochemical staining. Here, we found that atranorin inhibited glioma cell invasion and spheroid formation by downregulating epithelial-mesenchymal transition (EMT) and cancer stemness regulators and markers. The atranorin hydrolytic derivatives atraric acid and haematommic acid inhibited glioma cell invasiveness and stemness, respectively. Also, major oncogenic signaling pathways-Wnt, AP-1, STAT, Hedgehog, Notch, and NF-κB-were investigated, revealing that atranorin robustly decreased the transcriptional activities of TOPFLASH, AP-1, Gli, CBF1/Su(H)/Lag-1, hairy/enhancer of Split, and expression of the related downstream targets such as β-catenin, cyclin-D1, c-myc, c-Jun, c-Fos, Gli1, Gli2, Smoothened, and Notch 1 intracellular domain. Moreover, atranorin-mediated upregulation of Dusp3 and Ptpn1 suppressed the invasiveness and stemness of gliomas by dephosphorylating STAT and NF-κB. Importantly, atranorin exerts synergistic antiglioma effects on invasion and spheroid formation in combination treatment with temozolomide. These findings identified that atranorin could be developed as a specific therapy to target EMT and CSC pathways to suppress malignant behaviors in glioma.

Keywords: atranorin; atraric acid; glioma; haematommic acid; protein tyrosine phosphatase; temozolomide.

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References

    1. Ajani, J. A., S. Song, H. S. Hochster, and I. B. Steinberg. 2015. “Cancer Stem Cells: The Promise and the Potential, Seminars in Oncology.” Seminars in Oncology 42: S3–S17.
    1. Amand, M., C. Erpicum, K. Bajou, et al. 2014. “DUSP3/VHR Is a Pro‐Angiogenic Atypical Dual‐Specificity Phosphatase.” Molecular Cancer 13: 1–18.
    1. Ari, F., E. Ulukaya, S. Oran, S. Celikler, S. Ozturk, and M. Ozel. 2015. “Promising Anticancer Activity of a Lichen, Parmelia Sulcata Taylor, Against Breast Cancer Cell Lines and Genotoxic Effect on Human Lymphocytes.” Cytotechnology 67: 531–543.
    1. Azman, A. A., N. Nadiah, A. R. Rosandy, A. Alwi, N. Kamal, and R. Mohd. 2021. “Antimicrobial Activity and LC‐MS Data Comparison From Lichen Parmotrema Praesorediosum in Bangi, Selangor, Malaysia.” Sains Malaysiana 50: 383–393.
    1. Bhardwaj, R., A. Suzuki, P. Leland, B. H. Joshi, and R. K. Puri. 2018. “Identification of a Novel Role of IL‐13Rα2 in Human Glioblastoma Multiforme: Interleukin‐13 Mediates Signal Transduction Through AP‐1 Pathway.” Journal of Translational Medicine 16: 1–13.

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