Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma

Received 2 June 2009; received in revised form 5 October 2009; accepted 8 October 2009. published online 09 November 2009.

Abstract

Chronic ethanol consumption is a known risk factor for developing hepatocellular carcinoma (HCC). The use of plant-derived antioxidants is gaining increasing clinical prominence as a potential therapy to ameliorate the effects of ethanol on hepatic disease development and progression. This study demonstrates silibinin, a biologically active flavanoid derived from milk thistle, inhibits cytochrome p4502E1 induction, ethanol metabolism and reactive oxygen species generation in HCC cells in vitro. These silibinin-mediated effects also inhibit ethanol-dependent increases in HCC cell proliferation in culture.

Keywords: Hepatocellular carcinoma, Ethanol, Cytochrome P4502E1, Oxidative stress, Mitogenesis

a Department of Biology, The University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223, USA

b Department of General Surgery, Carolinas Medical Center, 1000 Blythe Blvd., Charlotte, NC 28203, USA

Corresponding author. Address: Department of General Surgery, Carolinas Medical Center, Cannon Research Building, Room 402, 1000 Blythe Blvd, Charlotte, NC 28203, USA. Tel.: +1 44 1 704 355 2846; fax: +1 44 1 704 355 7202.

PII: S0304-3835(09)00626-0

doi:10.1016/j.canlet.2009.10.004

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