Study of the Relationship between Sigma Receptor Expression Levels and Some Common Sigma Ligand Activity in Cancer Using Human Cancer Cell Lines of the NCI-60 Cell Line Panel

Sigma (sigma) receptors have attracted great interest since they are implicated in various cellular functions and biological processes and diseases, including various types of cancer. The receptor family consists of two subtypes: sigma-1 (sigma 1) and sigma-2 (sigma 2). Both sigma receptor subtypes have been proposed as therapeutic targets for various types of cancers, and many studies have provided evidence that their selective ligands (agonists and antagonists) exhibit antiproliferative and cytotoxic activity. Still, the precise mechanism of action of both sigma receptors and their ligands remains unclear and needs to be elucidated. In this study, we aimed to simultaneously determine the expression levels of both sigma receptor subtypes in several human cancer cell lines. Additionally, we investigated the in vitro antiproliferative activity of some widely used sigma 1 and sigma 2 ligands against those cell lines to study the relationship between sigma receptor expression levels and sigma ligand activity. Finally, we ran the NCI60 COMPARE algorithm to further elucidate the cytotoxic mechanism of action of the selected sigma ligands studied herein.

Automated summary

This study aimed to investigate the expression levels of both sigma receptor subtypes in several human cancer cell lines and study their relationship with the activity of sigma ligands. Through in vitro experiments and the NCI60 COMPARE algorithm, the cytotoxic mechanism of action of the selected sigma ligands studied herein was further elucidated.