Speaker Credentials
MS-II
Speaker Credentials
BS
College
College of Allopathic Medicine
Medical Specialty
Internal Medicine
Format
Poster
Start Date
November 2024
End Date
November 2024
Track
3
Abstract
Objective. Examine the role of curcumin analogs in modulating cell stress pathways and cytotoxicity. Background. Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded or misfolded proteins, can trigger programmed cell death in the setting of environmental stressors such as ROS, hypoxia, or acidosis. The unfolded protein response (UPR) is a cellular survival mechanism employed to alleviate ER stress. Notably, the pro-survival pathways of the UPR are upregulated in glioblastoma and are implicated in both chemoresistance and radiation resistance, making effective treatment more difficult. Modulation of the UPR is a promising therapeutic strategy for improving outcomes of patients diagnosed with glioblastoma, a tumor with a low survival rate. Methods. A series of curcumin derivatives were tested against three lines of glioblastoma stem-like cells (GSCs). Western blotting was performed to identify proteins targeted by the activity of such compounds on ER stress. Results. We identified a trimethoxy bis-chalcone curcumin derivative which was 100-fold more cytotoxic to GSCs compared to curcumin. Western blot analysis indicated that this bis-chalcone modulated the UPR by increasing pro-death C-EBP Homologous Protein (CHOP) expression and decreasing pro-survival chaperone GRP78/Bip expression. Furthermore, expression of activated caspase-7 and PARP cleavage indicated apoptotic activity. Conclusion. This bis-chalcone activates the pro-death arm of the UPR signaling pathway and is highly cytotoxic to radio- and chemo-resistant GSCs, while demonstrating no toxicity toward non-tumor cells. More investigation must be done to evaluate this compound’s effects on other cellular processes. Grants. This study was funded by HCA Florida University Hospital, Mystic Force Foundation.
Included in
Targeting ER Stress Pathways with Curcumin Analogs to Enhance Glioblastoma Stem Cell Death
Objective. Examine the role of curcumin analogs in modulating cell stress pathways and cytotoxicity. Background. Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded or misfolded proteins, can trigger programmed cell death in the setting of environmental stressors such as ROS, hypoxia, or acidosis. The unfolded protein response (UPR) is a cellular survival mechanism employed to alleviate ER stress. Notably, the pro-survival pathways of the UPR are upregulated in glioblastoma and are implicated in both chemoresistance and radiation resistance, making effective treatment more difficult. Modulation of the UPR is a promising therapeutic strategy for improving outcomes of patients diagnosed with glioblastoma, a tumor with a low survival rate. Methods. A series of curcumin derivatives were tested against three lines of glioblastoma stem-like cells (GSCs). Western blotting was performed to identify proteins targeted by the activity of such compounds on ER stress. Results. We identified a trimethoxy bis-chalcone curcumin derivative which was 100-fold more cytotoxic to GSCs compared to curcumin. Western blot analysis indicated that this bis-chalcone modulated the UPR by increasing pro-death C-EBP Homologous Protein (CHOP) expression and decreasing pro-survival chaperone GRP78/Bip expression. Furthermore, expression of activated caspase-7 and PARP cleavage indicated apoptotic activity. Conclusion. This bis-chalcone activates the pro-death arm of the UPR signaling pathway and is highly cytotoxic to radio- and chemo-resistant GSCs, while demonstrating no toxicity toward non-tumor cells. More investigation must be done to evaluate this compound’s effects on other cellular processes. Grants. This study was funded by HCA Florida University Hospital, Mystic Force Foundation.