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KMID : 0603520040090010026
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Journal of Korean Association of Cancer Prevention
2004 Volume.9 No. 1 p.26 ~ p.35
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Growth Inhibition of Human Lung Carcinoma Cells by β-lapachone through Induction of Apoptosis
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Lee Jae-Hun
Park Cheol
Choi Byung-Tae
Lee Won-Ho
Choi Yung-Hyun
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Abstract
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The DNA topoismerase I inhibitor β-lapachone, the product of a lapacho tree (Tabebuia avellanedae) from South America, activates a novel apoptotic response in a number of cell lines. In the present report, we investigated the effects of β-lapachone on the growth of human lung in human non-small-cell-lung-cancer A549 cells. Upon treatment with β-lapachone, a concentration-dependent inhibition of cell viability and cell proliferation was observed as measured by hemocytometer counts and MTT assay. The β-lapachone- treated cells developed many of the hallmark features of apoptosis, including membrane shrinking, condensation of chromatin and DNA fragmentation. These apoptotic effects of β-lapachone in A549 cells were associated with a marked induction of pro-apoptotic Bax expression, however the levels of anti-apoptotic Bcl-2 expression were decreased in a dose-dependent manner. Accordingly, elevated amount of cyclindependent kinase inhibitor p21 expression accompanied by up-regulation of tumor suppressor p53 was observed. By RT-PCR analyses, decrease in gene expression level of telomerase reverse transcriptase and telomeric repeat binding factor were also observed. Thus, these findings suggest that β-lapachone may be a potential anti-cancer therapeutics for the control of human lung cancer cell model.
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KEYWORD
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β-lapachone , Lung carcinoma, Apoptosis, Bax, Bcl-2
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