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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
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