Altered lipid profile, oxidative status and hepatitis B virus interactions in human hepatocellular carcinoma

Altered membrane integrity in hepatocellular carcinoma (HCC) tissue was indicated by an elevation in cholesterol and significant decrease in phosphatidylcholine (PC). The resultant decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) and increased cholesterol/phospholipid ratios are associated with decreased fluidity in the carcinoma tissue. The lower PC was associated with a decrease in the quantitative levels of the saturated (C16:0, C18:0), omega 6 (C18:2, C20:4) and omega 3 (C22:5, C22:6) fatty acids (FAs), resulting in reduced long-chain polyunsaturated fatty acids (LCPUFAs), total PUFA and an increase in omega 6/omega 3 FA ratio. In PE, the saturated and omega 3 (C22:5, C22:6) FAs were reduced while the total omega 3 FA level was not affected, leading to an increased omega 6/omega 3 FA ratio. Increased levels of C18:1 omega 9, C20:2 omega 6 and reduction of 22:6 omega 3 in PC and PE suggest a dysfunctional delta-6 desaturase. The reduced PC/PE ratio resulted in a decreased C20:4 omega 6 (PC/PE) ratio, implying a shift towards synthesis of the 2-series eicosanoids. Lipid peroxidation was reduced in both hepatitis B negative (HBV-) and positive (HBV+) HCC tissues. Glutathione (GSH) was decreased in HCC while HBV had no effect, suggesting an impairment of the GSH redox cycle. In contrast HBV infection enhanced GSH in the surrounding tissue possibly to counter oxidative stress as indicated by the increased level of conjugated dienes. Apart from the reduced LCPUFA, the low level of lipid peroxidation in the carcinoma tissue was associated with increased superoxide dismutase and glutathione peroxidase activity. The disruption of the redox balance, resulting in increased cellular antioxidant capacity, could create an environment for resistance to oxidative stress in the carcinoma tissue. Alterations in membrane cholesterol, phospholipids, FA parameters, C20:4 omega 6 membrane distribution and low lipid peroxidation are likely to be important determinants underlying the selective growth advantage of HCC cells. (C) 2009 Elsevier Ltd. All rights reserved.