4.7 Article

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

期刊

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 61, 期 18, 页码 4326-4335

出版社

AMER CHEMICAL SOC
DOI: 10.1021/jf4004175

关键词

lysyl oxidase; hepatocellular carcinoma; metastasis; pterostilbene; alcoholism

资金

  1. National Science Council [NSC 96-2628-B-038-003-MY3(1-3), NSC 98-2320-B-038-006-MY3(1-3), DOH99-TD-C-111-008, 97-2314-B-038-034-MY3(1-3)]
  2. Cathay Medical Center [100CGH-TMU-04, 97CGH-TMU-02]

向作者/读者索取更多资源

Ethanol consumption induces hepatocellular carcinoma (HCC) cell metastasis by changing the eactracellular 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 mu M) 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.

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