Redox modulation and human bile duct cancer inhibition by curcumin.

Abstract

Curcumin, a major component from tumeric and well-known dietary spice, possesses various pharmacological effects. The cancer chemoprevention effect is suggested to act through its pro-oxidant property. The study was to clarify effects of curcumin on cholangiocarcinoma cells, a cancer of the bile duct that refractory to chemotherapeutic drugs. We examined time-course of oxidant formation in relation to antitumor and the adaptive antioxidant response of the cells. Curcumin induced antiproliferation and apoptosis in KKU-M214 CCA cells with concentration- and time- dependent manners. The antiproliferative effect of curcumin was observed at concentrations as low as 3 microM and was not necessarily associated with oxidative stress, while induction of apoptosis required significant production of superoxide anion, suppression of cellular redox and collapse of mitochondrial transmembrane potential. Western blot analysis showed a temporal relationship between the suppression of nuclear NF-kappaB with Bcl-XL protein levels. Up-regulation of p53 and Bax was associated with marked oxidative stress and apoptosis. Curcumin also induced Nrf2 protein expression with up-regulation of gamma-glutamylcysteine ligase mRNA and increased cellular antioxidant, glutathione. The study suggests that curcumin could be developed into an effective chemoprevention against CCA.

• Authors: Bunliang Suphim, Auemduan Prawan, Upa Kukongviriyapan, Sarinya Kongpetch, Benjaporn Buranrat, Veerapol Kukongviriyapan
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) 2010 Aug-Sep Vol. 48 Issue 8-9 Pg. 2265-72 ISSN: 1873-6351 [Electronic] England
• PMID: 20510329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Antioxidants
• NF-kappa B
• RNA, Neoplasm
• Superoxides
• Glutathione
• Curcumin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Bile Duct Neoplasms (drug therapy)
• Blotting, Western
• Cell Line, Tumor
• Cell Nucleus (chemistry, metabolism)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cholangiocarcinoma (drug therapy)
• Curcumin (pharmacology)
• Dose-Response Relationship, Drug
• Glutathione (metabolism)
• Humans
• Membrane Potentials (drug effects)
• NF-kappa B (analysis, metabolism)
• Oxidation-Reduction
• RNA, Neoplasm (biosynthesis, isolation & purification)
• Reverse Transcriptase Polymerase Chain Reaction
• Superoxides (metabolism)