Harnessing the cellular “trash can” to fight cancer

June 18, 2019

Nomura, et al

Study co-authors associate professor Daniel Nomura, graduate student Jessica Spradlin, and associate professor Thomas Maimone.

A team of UC Berkeley scientists has published a new study in Nature Chemical Biology that investigates how nimbolide, a natural product derived from the neem tree, may function in impairing cancer pathogenicity. This study is part of a growing body of research that explores natural products for proteins that can directly aid tumor suppression.

“We discover here that nimbolide not only impairs cancer pathogenicity through stabilizing tumor suppressors, but that we can exploit nimbolide to also degrade and eliminate other cancer-causing proteins in cells for cancer therapy,” says co-author Dan Nomura, an associate professor in the Departments of Nutritional Sciences and Toxicology, Chemistry, and Molecular and Cell Biology.

Nomura is the director of the Novartis-Berkeley Center for Proteomics and Chemistry Technologies (NB-CPACT), a partnership between Novartis and Berkeley researchers that focuses on developing new technologies for the discovery of next-generation therapeutics. This is one of the first papers to come out of the collaboration, focusing on using an innovative technology that rapidly maps small-molecule protein targets—including those that have been considered "undruggable."

Neem (Azadirachta indica) is a plant that has been extensively explored by the scientific community for its diverse pharmacological and ethnobotanical potential. Nimbolide is a terpene—a compound produced by the neem tree’s metabolism. Nimbolide has already been shown to exert multiple therapeutic effects against the spread of a wide range of cancers. Nimbolide impairs cancer spread by modifying the signaling pathways that cause tumorous growths, but the mechanism by which it acts remains largely unknown.

Nomura, co-senior author associate professor Thomas Maimone in the Department of Chemistry, and their colleagues discovered how nimbolide targets proteins that impair breast cancer cell growth by utilizing a technique called activity-based protein profiling (ABPP), which uses chemical probes to search for binding hotspots in complex protein mixtures.

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