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Characterization of a novel proteasome inhibitor in SK-N-SH neuroblastoma: mechanism and synergy with targeted anti-tumor agents


Proteasome inhibitors are being used in the treatment of cancers. Bortezomib, for example, has been clinically approved for treatment of multiple myeloma. The success of Bortezomib has opened the door for assessing other proteasome inhibitors for potential antineoplastic properties. It is believed that proteasome inhibitors cause cell death via a ubiquitination-based mechanism. Pro-apoptotic sigma-2 receptors, much like ubiquitin, are found in numerous organs and tissue systems. Sigma-2 receptors are highly expressed in tumor cells compared to normal cells, making it possible to selectively target cancer cells while sparing normal healthy cells. Ubiquitin-proteasome systems are believed to play a role in modulating: the signaling mechanism of Siramesine –a sigma-2 receptor agonist—, and the anti-apoptotic effects of NF-kB. This study is focused on Compound L (Cpd L); a novel compound belonging to a class of recently synthesized macrocyclic proteasome inhibitors created by the Sello lab, at Brown University. Cpd L decreases the viability of SK-N-SH neuroblastoma cells, especially in combination with Siramesine. Cpd L also enhances the cytotoxic effects of Cetuximab— a monoclonal anti-body that binds to epidermal growth factor receptors, believed to be caspase dependent in accomplishing its proapoptotic functions


Koroma, Donald Christian, "Characterization of a novel proteasome inhibitor in SK-N-SH neuroblastoma: mechanism and synergy with targeted anti-tumor agents" (2014). Summer Research Symposium. Brown Digital Repository. Brown University Library.



  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …