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Long-term ethanol exposure-induced hepatocellular carcinoma cell migration and invasion through lysyl oxidase activation are attenuated by combined treatment with pterostilbene and curcumin analogues.

Abstract
Ethanol consumption induces hepatocellular carcinoma (HCC) cell metastasis by changing the extracellular matrix (ECM). Lysyl oxidase (LOX) catalyzes the cross-linkage of collagen or elastin in the ECM. LOX protein and mRNA overexpression (>21-fold compared with controls, n = 6) was detected in cirrhotic HCC patients with a history of alcoholism. LOX protein expression was induced in HCC cells after long-term treatment with ethanol (10 mM) for 20-40 passages (denoted E20-E40 cells). Pterostilbene (PSB, 1 μM) displayed significant potency to reduce LOX-mediated activity in E40 cells when combined with curcumin and its analogues. The ability of E40 cells to form colonies in soft agar was reduced by both genetic depletion of LOX and by chemical inhibitors of LOX expression. This study suggests that targeting LOX expression with food components such as PSB and curcumin may be a novel strategy to overcome ethanol-induced HCC cell metastasis in liver cancer patients.
AuthorsChing-Shui Huang, Chi-Tang Ho, Shih-Hsin Tu, Min-Hsiung Pan, Chien-Hui Chuang, Hui-Wen Chang, Chien-Hsi Chang, Chih-Hsiung Wu, Yuan-Soon Ho
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 61 Issue 18 Pg. 4326-35 (May 08 2013) ISSN: 1520-5118 [Electronic] United States
PMID23560895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • RNA, Messenger
  • Stilbenes
  • pterostilbene
  • Ethanol
  • Collagen
  • Elastin
  • Protein-Lysine 6-Oxidase
  • Curcumin
Topics
  • Adult
  • Aged
  • Alcoholism
  • Antineoplastic Agents (pharmacology)
  • Carcinoma, Hepatocellular (pathology)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Collagen (genetics, metabolism)
  • Curcumin (pharmacology)
  • Elastin (genetics, metabolism)
  • Ethanol (adverse effects)
  • Extracellular Matrix (drug effects, metabolism)
  • Female
  • Gene Expression Regulation
  • Humans
  • Laser Capture Microdissection
  • Liver Neoplasms (pathology)
  • Male
  • Middle Aged
  • Protein-Lysine 6-Oxidase (genetics, metabolism)
  • RNA, Messenger (genetics, metabolism)
  • Real-Time Polymerase Chain Reaction
  • Stilbenes (pharmacology)

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