Anticancer properties of sodium selenite in human glioblastoma cell cluster spheroids.

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.

• Authors: Sylvie Berthier, Josiane Arnaud, Pierre Champelovier, Edwige Col, Catherine Garrel, Cécile Cottet, Jean Boutonnat, François Laporte, Patrice Faure, Florence Hazane-Puch
• Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (J Trace Elem Med Biol) Vol. 44 Pg. 161-176 (Dec 2017) ISSN: 1878-3252 [Electronic] Germany
• PMID: 28965572 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier GmbH. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Cadherins
• RNA, Messenger
• Caspase 3
• CA9 protein, human
• Carbonic Anhydrase IX
• Sodium Selenite

Topics

• Antigens, Neoplasm (metabolism)
• Apoptosis (drug effects)
• Cadherins (metabolism)
• Carbonic Anhydrase IX (metabolism)
• Caspase 3 (metabolism)
• Cell Aggregation (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Fragmentation (drug effects)
• Enzyme Activation (drug effects)
• Epigenesis, Genetic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (drug therapy, genetics, pathology)
• Humans
• Necrosis
• Neoplasm Invasiveness
• RNA, Messenger (genetics, metabolism)
• Sodium Selenite (pharmacology, therapeutic use)
• Spheroids, Cellular (drug effects, pathology)