Stress, inflammation, cancer, and dementia: curcumin and CDDO as therapeutic agents
Location
Georgia
Start Date
12-5-2015 1:00 PM
Description
The lack of effective therapeutics has spurred a renewed interest in drugs derived from natural plants. For centuries, countries around the world have utilized plant-based compounds to treat people with dementia and cancer. Curcumin and CDDO-derived compounds are two of the most promising therapeutic agents that are naturally found and synthetically derived, respectively. The present study investigates the ability of curcumin and CDDO-methyl ester (CDDO-me) to suppress inflammation through the regulation of pro-inflammatory mediators NF-kB and Chitinase-3-like protein 1 (CHI3L1) in rat hippocampal embryonic astrocytes. We discovered that curcumin and CDDO-me lowered NF-kB expression in pretreated astrocytes in response to ZnSO4 and H2O2-induced oxidative stress. On the contrary, these drugs increased CHI3L1 expression in stressed astrocytes. The compounds were also examined for anti-cancer effects in multiple myeloma (MM) cancer cells. Both treatments demonstrated significant time and dose-dependent responses in a two-dimensional setting (uncoated 48-well plate). To more accurately capture the in vivo environment, we encapsulated MM cells in a 3-dimensional gelatin-based culture before treatment; we found that the drugs were much less toxic in these conditions. With these findings, we conclude that curcumin and CDDO-me exhibit cytoprotective effects in ROS-induced oxidative-stressed astrocytes by regulating pro-inflammatory mediators while effectively inducing cell death in MM cancer cells in a two-dimensional environment. By studying drug effects and their modes of action, we will gain a better understanding of the mechanisms that underlie neurodegenerative diseases and cancers. If these mechanisms can be identified, effective drugs can be designed to improve patient prognoses.
Stress, inflammation, cancer, and dementia: curcumin and CDDO as therapeutic agents
Georgia
The lack of effective therapeutics has spurred a renewed interest in drugs derived from natural plants. For centuries, countries around the world have utilized plant-based compounds to treat people with dementia and cancer. Curcumin and CDDO-derived compounds are two of the most promising therapeutic agents that are naturally found and synthetically derived, respectively. The present study investigates the ability of curcumin and CDDO-methyl ester (CDDO-me) to suppress inflammation through the regulation of pro-inflammatory mediators NF-kB and Chitinase-3-like protein 1 (CHI3L1) in rat hippocampal embryonic astrocytes. We discovered that curcumin and CDDO-me lowered NF-kB expression in pretreated astrocytes in response to ZnSO4 and H2O2-induced oxidative stress. On the contrary, these drugs increased CHI3L1 expression in stressed astrocytes. The compounds were also examined for anti-cancer effects in multiple myeloma (MM) cancer cells. Both treatments demonstrated significant time and dose-dependent responses in a two-dimensional setting (uncoated 48-well plate). To more accurately capture the in vivo environment, we encapsulated MM cells in a 3-dimensional gelatin-based culture before treatment; we found that the drugs were much less toxic in these conditions. With these findings, we conclude that curcumin and CDDO-me exhibit cytoprotective effects in ROS-induced oxidative-stressed astrocytes by regulating pro-inflammatory mediators while effectively inducing cell death in MM cancer cells in a two-dimensional environment. By studying drug effects and their modes of action, we will gain a better understanding of the mechanisms that underlie neurodegenerative diseases and cancers. If these mechanisms can be identified, effective drugs can be designed to improve patient prognoses.