Elucidating the Mechanism Whereby Native Hawaiian Plant Extracts Induce Calcium-dependent Cell Death in Drug-resistant Neuroblastoma

Background

The proposed research project investigates the effects of traditionally prepared Native Hawaiian (NH) plant extracts on ER calcium signaling in drug resistant Neuroblastoma. Native Hawaiian traditional medicine has been used for centuries to treat a variety of ailments. Despite its use by many local communities and Native Hawaiian traditional medicine practitioners, the efficacy and pharmacological activity of Hawaiian traditional medicine is not fully understood. 

Nathan Sunada will continue to work on this project, which identified NH traditional preparations of noni (Morinda citrifolia) and olena (Curcuma longa), as having anticancer activity. These extracts were able to halt NB cell growth and trigger NB cell death. Calcium signaling has been shown to have an important role in both of these processes and preliminary data show that ER calcium signaling is altered in drug resistant NB. MYCN gene amplification has been shown to regulate the expression of ER proteins. We believe that MYCN and ER calcium signaling are intimately connected and that both play a critical role in contributing to drug resistance in NB. 

Project Goal

This project evaluates the effects of NH preparations of noni and olena on calcium signaling in drug sensitive and drug resistant NB cells, with MYCN amplification. By identifying differences in the calcium response between different NB cell types, we may uncover new targets to reduce or reverse drug resistance. Our investigation into the effects of Hawaiian traditional medicine may also lead to the development of new anticancer agents to treat NB.