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http://dx.doi.org/10.5352/JLS.2005.15.3.323

Growth Inhibition of Human Hepatoma and Bladder Carcinoma Cells by DNA Topoisomerae Inhibitor β-lapachone  

Choi Da Yean (R&E Program, Busan Science Academy)
Lee Jae Il (R&E Program, Busan Science Academy)
Chung Hyun Sup (R&E Program, Busan Science Academy)
Seo Han Gyeol (R&E Program, Busan Science Academy)
Woo Hyun Joo (Department of Biochemistry, Dongeui University College of Oriental Medicine Busan)
Choi Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine Busan)
Publication Information
Journal of Life Science / v.15, no.3, 2005 , pp. 323-331 More about this Journal
Abstract
The objective of the present study was to investigate the effect of $\beta-lapachone$, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) in South America, on the cell growth of human hepatoma (HepG2) and bladder (T24) carcinoma cells. Exposure of cancer cells to $\beta-lapachone$ resulted in growth inhibition, morphological changes and apoptosis in a concentration-dependent manner, which could be proved by MTT assay and flow cytometry analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that $\beta-lapachone$ did not affect the levels of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAFl/CIPl) expression. However, the transcriptional factor Sp-l and proliferating cell nuclear antigen (PCNA) protein levels were significantly down-regulated by $\beta-lapachone$ in both cell lines. Moreover, $\beta-lapachone$ treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-l (TEP-l). Taken together, these findings suggest that $\beta-lapachone$-induced inhibition of human hepatoma and bladder carcinoma cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and provide important new insights into the additional mechanisms of the anti-cancer activity of $\beta-lapachone$.
Keywords
apoptosis; human hepatoma and bladder carcinoma cells;
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