Indole analogs and the aryl sulfonamide AqB011 potently restrain the invasiveness of glioblastoma cells, as determined in ex vivo xenograft tissue slice co-cultures (XTCCs).
8 affiliations
- 1School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, 5005, Australia.
- 2Rudolf-Boehm-Institute for Pharmacology and Toxicology, Medical Faculty, University of Leipzig, Härtelstrasse 16-18, Leipzig, D-04107, Germany.
- 3Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Medical Faculty, University of Leipzig, Härtelstrasse 16-18, Leipzig, D-04107, Germany.
- 4Institute for Biomedicine and Glycomics, Griffith University, Nathan, 4111, QLD, Australia.
- 5School of Environment and Science, Griffith University, Nathan, 4111, QLD, Australia.
- 6NatureBank, Griffith University, Nathan, 4111, QLD, Australia.
- 7Rudolf-Boehm-Institute for Pharmacology and Toxicology, Medical Faculty, University of Leipzig, Härtelstrasse 16-18, Leipzig, D-04107, Germany. [email protected].
- 8Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Medical Faculty, University of Leipzig, Härtelstrasse 16-18, Leipzig, D-04107, Germany. [email protected].
Abstract
Background
Glioblastomas (GBMs) are highly invasive and heterogeneous in nature which strongly contributes to poor survival of patients, averaging 15 months after diagnosis. With little treatment options being available in particular for addressing GBM invasiveness, there is a high need for supplementary therapies in addition to classical cytostatics like Temozolomide (TMZ).Methods
The aim of this study was to examine promising compounds, the natural indole scaffold RAD114 and three semisynthetic analogs (RAD118, RAD119, RAD120) as well as the aryl sulfonamide AqB011, for their inhibitory potential specifically on tumor cell invasion. For this, GBM xenograft tissue slice tandem co-culture (XTCC) models were employed, closely reflecting the in vivo patient situation. In particular, these ex vivo tissue slice air-liquid interface (ALI) models also allow for distinguishing between inhibitory effects on bulk tumor growth vs tumor cell invasion into the normal brain tissue.Results
Profound anti-invasive effects of the natural indole scaffold RAD114, three semisynthetic analogs (RAD118, RAD119, RAD120), and the aryl sulfonamide AqB011 were observed in XTCC models based on G55T2 and U87-MG GBM xenografts co-cultured with mouse brain slices in ALI tandem co-culture. While effects on bulk tumor growth were rather moderate, profound inhibition or even abolishment of tumor invasion was observed, dependent on the compound, its dosage and the model. At a non-toxic concentration (10 µM), RAD118 and AqB011 showed the highest effectiveness in reducing tumor invasion. Combination effects at sub-optimal compound dosages were observed as well.Conclusions
Both compound classes - the tested semisynthetic indole analogs and the sulfonamide derivative - may be promising lead candidates for drugs useful to specifically address the issue of GBM invasiveness. They strongly restrained GBM cell invasion, alone and in combination. Rather than acting through cytotoxic effects, they specifically inhibit cell migration into native brain tissue.
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BibTeX
@article{wagner2026indole,
title = {{Indole analogs and the aryl sulfonamide AqB011 potently restrain the invasiveness of glioblastoma cells, as determined in ex vivo xenograft tissue slice co-cultures (XTCCs).}},
author = {Kim K Wagner and Andrea J Yool and Rohan A Davis and Katrin Becker and Heike Franke and Achim Aigner},
journal = {Cancer cell international},
year = {2026},
month = oct,
doi = {10.1186/s12935-026-04489-8},
url = {https://europepmc.org/article/MED/42958353},
note = {CC BY},
}
RIS
TY - JOUR
TI - Indole analogs and the aryl sulfonamide AqB011 potently restrain the invasiveness of glioblastoma cells, as determined in ex vivo xenograft tissue slice co-cultures (XTCCs).
AU - Kim K Wagner
AU - Andrea J Yool
AU - Rohan A Davis
AU - Katrin Becker
AU - Heike Franke
AU - Achim Aigner
PY - 2026
DA - 2026/10/27
JO - Cancer cell international
DO - 10.1186/s12935-026-04489-8
UR - https://europepmc.org/article/MED/42958353
AB - Background Glioblastomas (GBMs) are highly invasive and heterogeneous in nature which strongly contributes to poor survival of patients, averaging 15 months after diagnosis. With little treatment options being available in particular for addressing GBM invasiveness, there is a high need for supplementary therapies in addition to classical cytostatics like Temozolomide (TMZ).Methods The aim of this study was to examine promising compounds, the natural indole scaffold RAD114 and three semisynthetic analogs (RAD118, RAD119, RAD120) as well as the aryl sulfonamide AqB011, for their inhibitory potential specifically on tumor cell invasion. For this, GBM xenograft tissue slice tandem co-culture (XTCC) models were employed, closely reflecting the in vivo patient situation. In particular, these ex vivo tissue slice air-liquid interface (ALI) models also allow for distinguishing between inhibitory effects on bulk tumor growth vs tumor cell invasion into the normal brain tissue.Results Profound anti-invasive effects of the natural indole scaffold RAD114, three semisynthetic analogs (RAD118, RAD119, RAD120), and the aryl sulfonamide AqB011 were observed in XTCC models based on G55T2 and U87-MG GBM xenografts co-cultured with mouse brain slices in ALI tandem co-culture. While effects on bulk tumor growth were rather moderate, profound inhibition or even abolishment of tumor invasion was observed, dependent on the compound, its dosage and the model. At a non-toxic concentration (10 µM), RAD118 and AqB011 showed the highest effectiveness in reducing tumor invasion. Combination effects at sub-optimal compound dosages were observed as well.Conclusions Both compound classes - the tested semisynthetic indole analogs and the sulfonamide derivative - may be promising lead candidates for drugs useful to specifically address the issue of GBM invasiveness. They strongly restrained GBM cell invasion, alone and in combination. Rather than acting through cytotoxic effects, they specifically inhibit cell migration into native brain tissue.
SN - 1475-2867
ER -