Manipulation of Curcumin Degradation to Enhance its Stability and Biological Activity

Abstract

Curcumin, a dietary compound from turmeric, is one of the most promising dietary compounds for cancer prevention and inflammation. However, curcumin rapidly degrades at physiological pH with a half‐life of several minutes, making it difficult to discern whether the cancer preventing and inflammation reducing effects are due to curcumin itself or its degradation products. In order to determine which compounds were most responsible for the observed anti‐cancer and anti‐inflammatory effects, we compared the biological activities of curcumin with a mixture of its stable total degradation products (TDP) and the most abundant stable degradation product, bicyclopentadione (BCP). We compared the effects of these compounds on cell proliferation, cell cycle progression, and apoptosis in MC38 colon cancer cells and lipopolysaccharide (LPS)‐induced inflammatory responses and NF‐kB signaling in RAW 264.7 macrophages. Our results showed that compared with curcumin, both TDP and BCP have dramatically reduced effects on cell proliferation, cell cycle progression and apoptosis in MC38 cells, and reduced effects on inhibition of inflammatory responses and NF‐kB signaling in RAW264.7 cells. These results suggest that the observed effects of curcumin are mainly mediated by curcumin itself, rather than its degradation products. We further showed that co‐addition of redox active antioxidants, which stabilizes curcumin in aqueous buffer, significantly enhanced the biological effects of curcumin in MC38 cells. Together, these results suggest that manipulation of curcumin degradation is a promising strategy to enhance its anti‐cancer and anti‐inflammatory effects.Support or Funding InformationArmstrong Fund of Science Award from University of Massachusetts Amherst and USDA NIFA 2016‐67017‐24423