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

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• 作者：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
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2013
• 出版时间：May 8, 2013
• 年：2013
• 卷：61
• 期：18
• 页码：4326-4335
• 全文大小：480K
• 年卷期：v.61,no.18(May 8, 2013)
• ISSN：1520-5118

文摘

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鈥?0 passages (denoted E20鈥揈40 cells). Pterostilbene (PSB, 1 渭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.

Keywords:

lysyl oxidase; hepatocellular carcinoma; metastasis; pterostilbene; alcoholism