Curcumin and 3’ 4’didemethylnobiletin in combination synergistically inhibit cell proliferation and potentiate apoptosis in HCT116 colon cancer cells (647.37)

Abstract

Curcumin and 3’, 4’ didemethylnobiletin (DDMN) a major metabolite of nobiletin, have each been shown to exhibit anti‐carcinogenic effects in various colon cancer models. However, the efficacy and molecular mechanisms of these dietary compounds in combination has yet to be explored. In this study the interaction of curcumin and DDMN was investigated in the HCT116 human colon cancer cells. Cell viability assays showed a greater inhibition of growth in cancer cells treated with the combination of curcumin and DDMN than with either treatment alone. Isobologram analysis confirmed the synergy between curcumin and DDMN in inhibiting colon cancer cell growth. Flow cytometry results revealed significant G2/M phase cell cycle arrest and extensive apoptosis induced by the combination, which were much stronger than the effects induced by the treatments with curcumin or DDMN alone. Pursuant to these findings, proteins associated with G2/M arrest and apoptosis were examined by Western Blot analysis to confirm increased expression levels of p21, p53, and C‐PARP, and decreased expression level of cdc2. Indeed, the change in expression of these proteins was much greater in response to the combination treatment of curcumin and DDMN than each compound alone. The synergy between curcumin and DDMN warrants further investigation on their combination to determine its chemopreventive potential for colorectal cancer in vivo.Grant Funding Source: Supported by NIH, AICR and USDA