Stress, inflammation, cancer, and dementia: curcumin and CDDO as therapeutic agents

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.