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Updated: Feb 22, 2026
A 3D Spheroid Model for Glioblastoma
Published on: April 9, 2020
Anticancer properties of sodium selenite in human glioblastoma cell cluster spheroids
Sylvie Berthier1, Josiane Arnaud2, Pierre Champelovier1
1Cytology Unit, Department of Anatomy and Pathologic Cytology (DACP), Institute of Biology and Pathology, Grenoble Alpes Hospital, CS10217, France.
Abstract:
Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared. SS impacts on proliferation, cell death, and invasiveness were evaluated as well as epigenetic modifications by focusing on histone deacetylase (HDAC) activity and dimethyl-histone-3-lysine-9 methylation (H3K9m2), after 24h to 72h SS exposition. SS was absorbed by spheroids and was more cytotoxic than TMZ (i.e., for LN229, the IC50 was 38 fold-more elevated for TMZ than SS, at 72h). SS induced a cell cycle arrest in the S phase and apoptosis via caspase-3. SS decreased carbonic anhydrase-9 (CA9) expression, invasion on a Matrigel matrix and modulated E- and N-Cadherin transcript expressions. SS decreased HDAC activity and modulated H3K9m2 levels. 3D model provides a relevant strategy to screen new drugs and SS is a promising drug against GBM that should now be tested in GBM animal models.
Insights
Sodium selenite (SS) shows significant anticancer effects against glioblastoma (GBM) in 3D cell models, proving more cytotoxic than temozolomide (TMZ). SS also inhibits GBM cell proliferation, invasion, and alters epigenetic markers, indicating its potential as a novel GBM therapeutic.
Area of Science:
- Oncology
- Neuro-oncology
- Drug Discovery
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
- Multicellular tumor spheroids (MCTS or 3D models) offer a more accurate in vivo tumor representation for drug screening.
- Sodium selenite (SS) is being explored for its potential anticancer properties.
Purpose of the Study:
- To investigate the anticancer effects of sodium selenite (SS) in 3D human glioblastoma (GBM) cell models.
- To compare the efficacy of SS with temozolomide (TMZ), the standard GBM treatment.
- To evaluate SS's impact on GBM cell proliferation, death, invasiveness, and epigenetic modifications.
Main Methods:
- Cultured three human GBM cell lines (LN229, U87, T98G) as multicellular tumor spheroids (MCTS).
- Assessed SS absorption, cytotoxicity, cell cycle arrest, apoptosis, and invasion.
- Evaluated epigenetic modifications including histone deacetylase (HDAC) activity and H3K9m2 levels after SS treatment.
Main Results:
- SS was absorbed by GBM spheroids and demonstrated significantly higher cytotoxicity than TMZ.
- SS induced S-phase cell cycle arrest and apoptosis via caspase-3 activation.
- SS reduced carbonic anhydrase-9 (CA9) expression, decreased invasion, and modulated E- and N-Cadherin expression.
- SS decreased HDAC activity and altered H3K9m2 levels, indicating epigenetic modulation.
Conclusions:
- The 3D MCTS model is a relevant platform for screening novel anti-GBM drugs.
- Sodium selenite (SS) exhibits promising therapeutic potential against glioblastoma (GBM) and warrants further investigation in animal models.
