Gedunin modulates cellular growth and apoptosis in glioblastoma cell lines.

BACKGROUND: Glioblastomas are characterized by aggressive behavior. Surgery, radiotherapy, and alkylating agents, including temozolomide are the most common treatment options for glioblastoma. Often, conventional therapies fail to treat these tumors since they develop drug resistance. There is a need for newer agents to combat this deadly tumor. Natural products such as gedunin have shown efficacy in several human diseases. A comprehensive study of gedunin, an heat shock protein (HSP)90 inhibitor, has not been thoroughly investigated in glioblastoma cell lines with different genetic modifications. AIMS: A key objective of this study was to determine how gedunin affects the biological and signaling mechanisms in glioblastoma cells, and to determine how those mechanisms affect the proliferation and apoptosis of glioblastoma cells. METHODS: The viability potentials of gedunin were tested using MTT, cell counts, and wound healing assays. Gedunin's effects on glioma cells were further validated using LDH and colony formation assays. In addition, we investigated the survival and apoptotic molecular signaling targets perturbed by gedunin using Western blot analysis and flow cytometry. RESULTS: Our results show that there was a reduction in cell viability and inhibition of wound healing in the cells tested. Western blot analysis of the gene expression data revealed genes such as EGFR and mTOR/Akt/NF kappa B to be associated with gedunin sensitivity. Gedunin treatment induced apoptosis by cleaving poly ADP-ribose polymerase, activating caspases, and downregulating BCL-xL. Based on these results, gedunin suppressed cell growth and HSP client proteins, resulting in apoptosis in glioblastoma cell lines. CONCLUSION: Our data provide in vitro support for the anticancer activity of gedunin in glioma cells by downregulating cancer survival proteins.

The impact of a provider motivational interviewing-based training on chronic pain management in a federally-qualified health center.

BACKGROUND: While the issue of opioid misuse is very complex, pharmacists have a unique opportunity to participate in interprofessional, team-based care. Motivational interviewing (MI) has been shown to be effective in chronic disease management and could improve patient engagement and chronic pain outcomes. OBJECTIVES: To determine the impact of an MI-based provider training on changes in chronic pain management prescribing and on provider and patient perceptions. METHODS: Providers participated in a pharmacist-led, 4-session educational intervention covering the CDC opioid prescribing guidelines, pain management, clinical pearls, and MI. Providers were then asked to implement the training in patient appointments for chronic pain management and refer appropriate patients for follow-up on goals. In the follow-up, student pharmacists called patients twice monthly for three months using MI. To address the primary outcome, the number of opioid prescriptions, morphine daily equivalents, and naloxone prescriptions were recorded and compared from the electronic medical record for the year preceding and following the intervention. Patients and providers completed surveys to assess the impact of these interventions. RESULTS: Providers (n = 11) reported increased confidence in MI from baseline to 12 months following the intervention but no change in satisfaction. Patients (n = 19) were able to set and accomplish 20 goals throughout the phone call intervention. Meanwhile, the number of opioid prescriptions significantly decreased from 569 to 368 prescriptions per year before and after the intervention, respectively. Morphine daily equivalents per prescription decreased from 26.8 to 26.4 for the year before versus the year following the intervention. CONCLUSIONS: MI interventions for providers and patients may positively impact goal setting and opioid prescribing. However, MI alone may not successfully address provider satisfaction and patient physical functioning. Pain management is an area that may benefit from a multi-faceted, interprofessional approach.