18β-Glycyrrhetinic Acid Exerts Subgroup-Specific Antitumor Activity and Enhances Radiosensitivity in Medulloblastoma.
- 1Biotechnologies Division, Department for Sustainability, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123 Rome, Italy.
- 2Radiation Systems and Application Division, Nuclear Department, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123 Rome, Italy.
Abstract
Background
Radiotherapy (RT) is a cornerstone of medulloblastoma (MB) treatment, but its efficacy may be limited by intrinsic or acquired radioresistance, while radiation-related late effects remain a major concern in pediatric patients. 18β-Glycyrrhetinic acid (18β-GA), a bioactive triterpenoid derived from Glycyrrhiza glabra, has shown antitumor activity in several malignancies. This study evaluated its antitumor and radiosensitizing effects in biologically distinct MB models.Methods
DAOY cells, used as an SHH-associated, TP53-mutant model, and D283 cells, commonly considered a Group 3/Group 4-associated model, were treated with 18β-GA (2.5-5 μM), γ-radiation (2-4 Gy), or their combination. Cell viability, clonogenic survival and migration were assessed. Apoptosis was evaluated by caspase-3/7 activity and cleaved caspase-3 expression. Modulation of AMPK/NF-κB and SHH signaling was examined by immunoblotting and RT-qPCR.Results
18β-GA reduced cell viability in a dose- and time-dependent manner and significantly reduced wound closure in DAOY cells and migratory capacity in D283 cells. D283 cells showed greater apoptotic sensitivity, accompanied by increased total and phosphorylated AMPK and reduced NF-κB p65 expression. In DAOY cells, 18β-GA reduced the expression of SHH-associated transcriptional markers, including GLI1, SOX2, CCND1, and MYC. Most importantly, 18β-GA significantly enhanced radiation response in both cell lines, producing greater reductions in viability and clonogenic survival than irradiation alone (p < 0.01). Combined treatment with 5 μM 18β-GA and 4 Gy reduced the surviving fraction to 0.013 in DAOY cells and approximately 0.01 in D283 cells (p < 0.001 versus radiation alone). This radiosensitizing effect was accompanied by increased caspase-3/7 activity and cleaved caspase-3 expression.Conclusions
18β-GA exerts antitumor activity in biologically distinct MB models through differential modulation of SHH and AMPK/NF-κB signaling, while converging on enhanced apoptotic susceptibility and a profound loss of clonogenic survival after irradiation. These findings provide a strong rationale for further preclinical evaluation of 18β-GA as a potential radiosensitizing adjuvant in MB.
Related
- Type-, dose-, and subgroup-specific associations of dairy intake with depressive and anxiety symptoms among middle school students
- 18β-glycyrrhetinic acid breaks the growth-immunity trade-off via selective suppression of adaptive immunity
- Targeting REV7 confers cervical cancer cell radiosensitivity and ferroptosis by negatively regulating SFXN1
- Mechanism of Glycyrrhiza and glycyrrhetinic acid in cisplatin-induced acute kidney injury: a proteomics and metabolomics study
- Single-strand break repair pathway disruption impacts radiosensitivity to both low- and high-LET radiation
BibTeX
@article{palone202618βglycyrrhetinic,
title = {{18β-Glycyrrhetinic Acid Exerts Subgroup-Specific Antitumor Activity and Enhances Radiosensitivity in Medulloblastoma.}},
author = {Francesca Palone and Luca Marchetti and Marco Corso and Emiliano Fratini and Ilaria De Stefano and Ilaria Di Sarcina and Simonetta Pazzaglia and Mariateresa Mancuso},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193233},
url = {https://europepmc.org/article/MED/42882928},
note = {CC BY},
}
RIS
TY - JOUR
TI - 18β-Glycyrrhetinic Acid Exerts Subgroup-Specific Antitumor Activity and Enhances Radiosensitivity in Medulloblastoma.
AU - Francesca Palone
AU - Luca Marchetti
AU - Marco Corso
AU - Emiliano Fratini
AU - Ilaria De Stefano
AU - Ilaria Di Sarcina
AU - Simonetta Pazzaglia
AU - Mariateresa Mancuso
PY - 2026
DA - 2026/10/08
JO - Cancers
DO - 10.3390/cancers18193233
UR - https://europepmc.org/article/MED/42882928
AB - Background Radiotherapy (RT) is a cornerstone of medulloblastoma (MB) treatment, but its efficacy may be limited by intrinsic or acquired radioresistance, while radiation-related late effects remain a major concern in pediatric patients. 18β-Glycyrrhetinic acid (18β-GA), a bioactive triterpenoid derived from Glycyrrhiza glabra, has shown antitumor activity in several malignancies. This study evaluated its antitumor and radiosensitizing effects in biologically distinct MB models.Methods DAOY cells, used as an SHH-associated, TP53-mutant model, and D283 cells, commonly considered a Group 3/Group 4-associated model, were treated with 18β-GA (2.5-5 μM), γ-radiation (2-4 Gy), or their combination. Cell viability, clonogenic survival and migration were assessed. Apoptosis was evaluated by caspase-3/7 activity and cleaved caspase-3 expression. Modulation of AMPK/NF-κB and SHH signaling was examined by immunoblotting and RT-qPCR.Results 18β-GA reduced cell viability in a dose- and time-dependent manner and significantly reduced wound closure in DAOY cells and migratory capacity in D283 cells. D283 cells showed greater apoptotic sensitivity, accompanied by increased total and phosphorylated AMPK and reduced NF-κB p65 expression. In DAOY cells, 18β-GA reduced the expression of SHH-associated transcriptional markers, including GLI1, SOX2, CCND1, and MYC. Most importantly, 18β-GA significantly enhanced radiation response in both cell lines, producing greater reductions in viability and clonogenic survival than irradiation alone (p < 0.01). Combined treatment with 5 μM 18β-GA and 4 Gy reduced the surviving fraction to 0.013 in DAOY cells and approximately 0.01 in D283 cells (p < 0.001 versus radiation alone). This radiosensitizing effect was accompanied by increased caspase-3/7 activity and cleaved caspase-3 expression.Conclusions 18β-GA exerts antitumor activity in biologically distinct MB models through differential modulation of SHH and AMPK/NF-κB signaling, while converging on enhanced apoptotic susceptibility and a profound loss of clonogenic survival after irradiation. These findings provide a strong rationale for further preclinical evaluation of 18β-GA as a potential radiosensitizing adjuvant in MB.
SN - 2072-6694
ER -