Format

Send to:

Choose Destination
See comment in PubMed Commons below
Int J Cancer. 2011 Jul 1;129(1):88-100. doi: 10.1002/ijc.25656. Epub 2010 Nov 3.

Curcumin decreases cholangiocarcinogenesis in hamsters by suppressing inflammation-mediated molecular events related to multistep carcinogenesis.

Author information

  • 1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Abstract

Cholangiocarcinoma (CCA) is a highly metastatic tumor linked to liver fluke infection and consumption of nitrosamine-contaminated foods and is a major health problem especially in South-Eastern Asia. In search for a suitable chemopreventive agents, we investigated the effect of curcumin, a traditional anti-inflammatory agent derived from turmeric (Curcuma longa), on CCA development in an animal model by infection with the liver fluke Opisthorchis viverrini and administration of N-nitrosodimethylamine and fed with curcumin-supplemented diet. The effect of curcumin-supplemented diet on histopathological changes and survival were assessed in relation to NF-κB activation, and the expression of NF-κB-related gene products involved in inflammation, DNA damage, apoptosis, cell proliferation, angiogenesis and metastasis. Our results showed that dietary administration of this nutraceutical significantly reduced the incidence of CCA and increased the survival of animals. This correlated with the suppression of the activation of transcription factors including NF-κB, AP-1 and STAT-3, and reduction in the expression of proinflammatory proteins such as COX-2 and iNOS. The formation of iNOS-dependent DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine) was inhibited. Curcumin suppressed the expression of proteins related to cell survival (bcl-2 and bcl-xL), proliferation (cyclin D1 and c-myc), tumor invasion (MMP-9 and ICAM-1) and angiogenesis (VEGF), and microvessel density. Induction of apoptotic events as indicated by caspase activation and PARP cleavage was also noted. Our results suggest that curcumin exhibits an anticarcinogenic potential via suppression of various events involved in multiple steps of carcinogenesis, which is accounted for by its ability to suppress proinflammatory pathways.

Copyright © 2010 UICC.

PMID:
20824699
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk