Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity

Cancer is a multifactorial disease that may be tackled by targeting different signaling pathways. Heme oxygenase-1 (HO-1) and sigma receptors (sigma Rs) are both overexpressed in different human cancers, including prostate and brain, contributing to the cancer spreading. In the present study, we investigated whether HO-1 inhibitors and sigma R ligands, as well a combination of the two, may influence DU145 human prostate and U87MG human glioblastoma cancer cells proliferation. In addition, we synthesized, characterized, and tested a small series of novel hybrid compounds (HO-1/sigma Rs) 1-4 containing the chemical features needed for HO-1 inhibition and sigma R modulation. Herein, we report for the first time that targeting simultaneously HO-1 and sigma R proteins may be a good strategy to achieve increased antiproliferative activity against DU145 and U87MG cells, with respect to the mono administration of the parent compounds. The obtained outcomes provide an initial proof of concept useful to further optimize the structure of HO-1/sigma Rs hybrids to develop novel potential anticancer agents.

Automated summary

Targeting both HO-1 and sigma R proteins simultaneously may provide an effective strategy for treating prostate and brain cancers, leading to increased antiproliferative activity. By synthesizing novel hybrid compounds, further optimization of structure can be achieved to develop more potent anticancer agents.