Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis.

Published

Journal Article

Pancreatic carcinoma is a lethal malignancy, with the best available therapeutic option-gemcitabine-yielding response rates of < 10%. Because nuclear factor-kappaB (NF-kappaB) has been determined to play a role in cell survival/proliferation in human pancreatic carcinoma, this transcription factor is a potential therapeutic target.The authors investigated the ability of curcumin (diferuloylmethane), an agent that is pharmacologically safe in humans, to modulate NF-kappaB activity.NF-kappaB and IkappaB kinase (IKK) were constitutively active in all human pancreatic carcinoma cell lines examined, and curcumin consistently suppressed NF-kappaB binding (as assessed using an electrophoretic mobility gel-shift assay) and IKK activity. Curcumin decreased the expression of NF-kappaB-regulated gene products, including cyclooxygenase-2 (as assessed using immunoblot analysis), prostaglandin E2, and interleukin-8 (as assessed using an enzyme-linked immunoassay), all of which have been implicated in the growth and invasiveness of pancreatic carcinoma. These changes were associated with concentration- and time-dependent antiproliferative activity (as assessed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay) and proapoptotic effects (as assessed via annexin V/propidium iodide staining [fluorescence-activated cell sorting, as well as with the induction of polyadenosine-5'-diphosphate-ribose polymerase cleavage).Curcumin down-regulated NF-kappaB and growth control molecules induced by NF-kappaB in human pancreatic cells. These effects were accompanied by marked growth inhibition and apoptosis. Through these findings, the authors provided a biologic rationale for the treatment of patients with pancreatic carcinoma using this nontoxic phytochemical.

Full Text

Duke Authors

Cited Authors

  • Li, L; Aggarwal, BB; Shishodia, S; Abbruzzese, J; Kurzrock, R

Published Date

  • November 2004

Published In

Volume / Issue

  • 101 / 10

Start / End Page

  • 2351 - 2362

PubMed ID

  • 15476283

Pubmed Central ID

  • 15476283

Electronic International Standard Serial Number (EISSN)

  • 1097-0142

International Standard Serial Number (ISSN)

  • 0008-543X

Digital Object Identifier (DOI)

  • 10.1002/cncr.20605

Language

  • eng