Identification of Nitro-Containing Compounds as Potent Inhibitors of Glioblastoma Stem Cells via STAT3 Pathway Suppression
Speaker Credentials
MDII
Speaker Credentials
MD
College
College of Allopathic Medicine
Medical Specialty
Neurosurgery
Format
Poster
Start Date
November 2024
End Date
November 2024
Track
3
Abstract
Identification of Nitro-Containing Compounds as Potent Inhibitors of Glioblastoma Stem Cells via STAT3 Pathway Suppression Matthew C. Pate1, Roberto Martin2, Emma Baker1, Blake Hutchins1, Maria Moreno Hollweg1, Sabrin Safar1, Kyuree Chang1, Eduardo A. Veliz PhD3, Steven Vanni DO 1,4, Regina M. Graham PhD1 1Nova Southeastern University Dr. Kiran C Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA, 2Nova Southeastern University Dr. Kiran C Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA, 3Department of Chemistry, University of Miami, Coral Gables, FL, USA ,4HCA Florida University Hospital, Davie, FL, USA, Objective: To examine cytotoxic effects of a series of nitro-compounds on GSCs to identify a lead compound for adjuvant GBM therapy. Introduction: Glioblastoma multiforme (GBM) is the most lethal and common primary malignant adult brain tumor. Despite current treatments, the five-year survival rate remains under 10%. Treatment-resistant glioblastoma stem cells (GSCs), responsible for the tumor's heterogeneity and post-therapy recurrence, are partially responsible for dismal outcomes. Nitro-group containing compounds, which have strong electron-withdrawing capabilities, are being explored as anti-cancer compounds. Methods: 41 nitro-containing chalcones and cyclic C5-curcumin analogs were synthesized and tested for cytotoxicity against GSC lines. GSCs were treated with 0.1-10 µM and viability was examined 72 hours later by MTS assay. Active compounds, an IC50 value of < 10 µM, were tested against human non-tumor cell lines. Western blot analysis was performed on these compounds to determine a mechanism of action. Outcomes: Of 41 compounds tested, over half had an average GSC IC50 value of ≤10 µM, and 4 compounds had an IC50 value in the lower nanomolar range. The most effective compounds were the cyclic C5-curcumin analogs. Western blot analysis identified the STAT3 signaling pathway as a likely target. Conclusion: The nitro-group is a potent and versatile functional group known to induce cancer cell death by several mechanisms. We identified several promising lead compounds with potent anti-GSC activity. Given its role in cancer stem cell maintenance and immune modulation, the STAT3 pathway is a promising therapeutic target for GBM. Funding: HCA Florida University Hospital, Mystic Force Foundation.
Identification of Nitro-Containing Compounds as Potent Inhibitors of Glioblastoma Stem Cells via STAT3 Pathway Suppression
Identification of Nitro-Containing Compounds as Potent Inhibitors of Glioblastoma Stem Cells via STAT3 Pathway Suppression Matthew C. Pate1, Roberto Martin2, Emma Baker1, Blake Hutchins1, Maria Moreno Hollweg1, Sabrin Safar1, Kyuree Chang1, Eduardo A. Veliz PhD3, Steven Vanni DO 1,4, Regina M. Graham PhD1 1Nova Southeastern University Dr. Kiran C Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA, 2Nova Southeastern University Dr. Kiran C Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA, 3Department of Chemistry, University of Miami, Coral Gables, FL, USA ,4HCA Florida University Hospital, Davie, FL, USA, Objective: To examine cytotoxic effects of a series of nitro-compounds on GSCs to identify a lead compound for adjuvant GBM therapy. Introduction: Glioblastoma multiforme (GBM) is the most lethal and common primary malignant adult brain tumor. Despite current treatments, the five-year survival rate remains under 10%. Treatment-resistant glioblastoma stem cells (GSCs), responsible for the tumor's heterogeneity and post-therapy recurrence, are partially responsible for dismal outcomes. Nitro-group containing compounds, which have strong electron-withdrawing capabilities, are being explored as anti-cancer compounds. Methods: 41 nitro-containing chalcones and cyclic C5-curcumin analogs were synthesized and tested for cytotoxicity against GSC lines. GSCs were treated with 0.1-10 µM and viability was examined 72 hours later by MTS assay. Active compounds, an IC50 value of < 10 µM, were tested against human non-tumor cell lines. Western blot analysis was performed on these compounds to determine a mechanism of action. Outcomes: Of 41 compounds tested, over half had an average GSC IC50 value of ≤10 µM, and 4 compounds had an IC50 value in the lower nanomolar range. The most effective compounds were the cyclic C5-curcumin analogs. Western blot analysis identified the STAT3 signaling pathway as a likely target. Conclusion: The nitro-group is a potent and versatile functional group known to induce cancer cell death by several mechanisms. We identified several promising lead compounds with potent anti-GSC activity. Given its role in cancer stem cell maintenance and immune modulation, the STAT3 pathway is a promising therapeutic target for GBM. Funding: HCA Florida University Hospital, Mystic Force Foundation.