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

Ching 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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4326-4335
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Volume61
Issue number18
DOIs
Publication statusPublished - May 8 2013

Keywords

  • alcoholism
  • hepatocellular carcinoma
  • lysyl oxidase
  • metastasis
  • pterostilbene

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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