Skip to main content
Journal cover image

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.

Publication ,  Journal Article
Li, L; Aggarwal, BB; Shishodia, S; Abbruzzese, J; Kurzrock, R
Published in: Cancer
November 15, 2004

BACKGROUND: 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. METHODS: The authors investigated the ability of curcumin (diferuloylmethane), an agent that is pharmacologically safe in humans, to modulate NF-kappaB activity. RESULTS: 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). CONCLUSIONS: 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

November 15, 2004

Volume

101

Issue

10

Start / End Page

2351 / 2362

Location

United States

Related Subject Headings

  • Protein Serine-Threonine Kinases
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Interleukin-8
  • Immunoblotting
  • I-kappa B Kinase
  • Humans
  • Enzyme-Linked Immunosorbent Assay
  • Electrophoretic Mobility Shift Assay
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, Lan, Bharat B. Aggarwal, Shishir Shishodia, James Abbruzzese, and Razelle Kurzrock. “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.Cancer 101, no. 10 (November 15, 2004): 2351–62. https://doi.org/10.1002/cncr.20605.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

November 15, 2004

Volume

101

Issue

10

Start / End Page

2351 / 2362

Location

United States

Related Subject Headings

  • Protein Serine-Threonine Kinases
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Interleukin-8
  • Immunoblotting
  • I-kappa B Kinase
  • Humans
  • Enzyme-Linked Immunosorbent Assay
  • Electrophoretic Mobility Shift Assay