Retracted: Notch‐1 down‐regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells

Abstract

BACKGROUND: Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of pancreatic cancer. Therefore, the down‐regulation of Notch signaling may be a novel approach for pancreatic cancer therapy. It has been reported that curcumin down‐regulates many genes that are known to promote survival and also up‐regulates genes that are known promoters of apoptosis in pancreatic cancer cells in vitro. It also has been reported that there is cross‐talk between Notch‐1 and another major cell growth and apoptotic regulatory pathway, the nuclear factor κB (NF‐κB) pathway, which is down‐regulated by both curcumin and reduction of Notch‐1 levels. However, to the authors' knowledge to date, no studies have determined whether the down‐regulation of Notch‐1 signaling, resulting in the inactivation of NF‐κB activity, contributes to curcumin‐induced cell growth inhibition and apoptosis in pancreatic cancer cells. METHODS: The authors used multiple molecular approaches, such as the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, an apoptosis assay, gene transfection, real‐time reverse transcriptase‐polymerase chain reaction analysis, Western blot analysis, and an electrophoretic mobility shift assay to measure the DNA binding activity of NF‐κB. RESULTS: Curcumin inhibited cell growth and induced apoptosis in pancreatic cancer cells. Notch‐1, Hes‐1, and Bcl‐X L expression levels concomitantly were down‐regulated by curcumin treatment. These results correlated with the inactivation of NF‐κB activity and increased apoptosis induced by curcumin. The down‐regulation of Notch‐1 by small‐interfering RNA prior to curcumin treatment resulted in enhanced cell growth inhibition and apoptosis. CONCLUSIONS: The current results provide the first demonstration to the authors' knowledge that the Notch‐1 signaling pathway is associated mechanistically with NF‐κB activity during curcumin‐induced cell growth inhibition and apoptosis of pancreatic cells. These results suggest that the down‐regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with pancreatic cancer. Cancer 2006. © 2006 American Cancer Society.