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The objective of the present study was to investigate the effect of β-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 β-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 β-lapachone did not affect the levels of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression. However, the transcriptional factor Sp-1 and proliferating cell nuclear antigen (PCNA) protein levels were significantly down-regulated by β-lapachone in both cell lines. Moreover, β-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-1 (TEP-1). Taken together, these findings suggest that β-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 β-lapachone.
목차
Abstract
재료 및 방법
결과 및 고찰
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참고문헌
참고문헌 (37)
참고문헌 신청
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Capranico, G., G. Zagotto and M. Palumbo. 2004. Development of DNA topoisomerase-related therapeutics: a short perspective of new challenges. Curr. Med. Chem. Anti-Canc. Agents 4, 335-345.
Bakshi, R. P. and T. A. Shapiro. 2003. DNA topoisomerases as targets for antiprotozoal therapy. Mini Rev. Med. Chem. 3, 597-608.
Bellamy, W. T. 1992. Prediction of response to drug therapy of cancer. A review of in vitro assays. Drugs 44, 690-708.
Biggs, J. R., J. E. Kudlow and A. S. Kraft. 1996. The role of the transcription factor Sp1 in regulating the expression of the WAF1/CIP1 gene in U937 leukemic cells. J. Biol. Chem. 271, 901-906.
Capranico, G., G. Zagotto and M. Palumbo. 2004. Development of DNA topoisomerase-related therapeutics: a short perspective of new challenges. Curr. Med. Chem. Anti-Canc. Agents 4, 335-345.
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UCI(KEPA) : I410-ECN-0101-2009-470-015374979