beta-Lapachone induced cell death in human hepatoma (HepA2) cells

In present study we studied the cytotoxic effects of beta-lapachone, a potent anticancer drug, on the human hepatoma cell line (HepA2) under serum-free condition. Most cells died after 2 microM beta-lapachone addition at 48 hours. No apoptotic characteristics of DNA ladder was documented by agarose DNA electrophoresis. The blockage of cell cycle at S phase and unscheduled DNA synthesis were demonstrated by flow cytometric analysis and anti-bromodeoxyuridine immunocytochemistry. Ultrastructural observation showed that the swollen mitochondria, dilatation and vesiculation of rER and proliferation of peroxisome-like granules appeared within the cytoplasm of HepA2 cells following drug treatment. Using enzyme cytochemistry, both peroxidase and acid phosphatase activities but not catalase activity were localised in these peroxisome-like granules. Therefore, these results suggested that (a) beta-lapachone has a novel cytotoxic effect on human hepatoma cell; (2) beta-lapachone induces the interruption of the cell cycle and unscheduled DNA synthesis in HepA2 cells; and (3) beta-lapachone promotes the proliferation of peroxisome-like granules containing peroxidase and acid phosphatase activities without evidence of catalase activity in hepatoma cell line.