HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology



ß-lapachone induced cell death in human hepatoma (HepA2) cells

C.-C. Lai1, T.-J. Liu2, L.-K. Ho3, M-J. Don4 and Y.-P. Chau1

1Institute of Anatomy, 2Department of Physical Medicine and Rehabititation and 3Department of Pharmacology, National Yang-Ming University and 4National Research Institute of Chine Medicine, Taipei, Republic of China

Offprint requests to: Dr. Yat-Pang Chau, Ph.D., Institute of Anatomy, School of Life Science, National Yang-Ming University, 155, 2nd Sec., Li-Nung Street, Shih-Pai, Taipei, Taiwan 112, Republic of China

 

Summary. In present study we studied the cytotoxic effects of ß-lapachone, a potent anticancer drug, on the human hepatoma cell line (HepA2) under serum-free condition. Most cells died after 2 µM ß-lapachone addition at 48 hours. No apoptotic characteristics of DNA ladder was documented by agarose DNA electro-phoresis. 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) ß-lapachone has a novel cytotoxic effect on human hepatoma cell; (2) ß-lapachone induces the interruption of the cell cycle and unscheduled DNA synthesis in HepA2 cells; and (3) ß-lapachone promotes the proliferation of peroxisome-like granules containing peroxidase and acid phosphatase activities without evidence of catalase activity in hepatoma cell line. Histol Histopathol 13, 89-97 (1998)

 

Key words: Hepatoma cells, ß-lapachone, Cell death, Electron microsocpy, Flow cytometry

DOI: 10.14670/HH-13.89