Identifying neuronal damage biomarkers in Bortezomib-induced peripheral neuropathy (BIPN)

Identifying neuronal damage biomarkers in Bortezomib-induced peripheral neuropathy (BIPN)

Multiple myeloma is the second most common hematological cancer of plasma cells. Bortezomib (BTZ) is a proteasome complex inhibitor commonly used as a chemotherapeutic agent to treat multiple myeloma patients. However, it also known to cause a dose-limiting toxicity known as BTZ-induced peripheral neuropathy (BIPN). The aim of this study is to determine the BTZ-induced neuronal damage, identifying biomarkers of neurotoxicity, and testing novel strategies for its prevention or reversal. In our preliminary studies, we utilized PC12 cells as the in vitro neuronal model. These studies included culturing and differentiating PC12 cells using nerve growth factor (NGF) at 100 ng/ml concentration for 7 days. Undifferentiated and differentiated PC12 cells were treated with BTZ for 24 hours, followed by western blot analysis for the neuronal damage biomarkers such as cyclic AMP response element binding (CREB) protein and Neuron-specific enolase (NSE). Our results showed increased expression of and NSE confirming the neuronal damage in BTZ treated samples. The differences in the expression pattern of these biomarkers were quantified using the ImageJ software. We will be further investigating the effects of various neuroprotective strategies such as the use of vitamin B12, gamma linolenic acid (GLA), and low level laser treatment (LLLT) to prevent or reverse the chemo-induced neuronal damagein BTZ treated PC12 cells. (This project was supported by the President’s Faculty Research andDevelopment Grant from NSU and the generous financial support from The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida).