Growth inhibition of A549 human lung carcinoma cells by beta-lapachone through induction of apoptosis and inhibition of telomerase activity.
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), on the cell growth and apoptosis in human lung carcinoma cell line A549. Exposure of A549 cells to beta-lapachone resulted in growth inhibition and induction of apoptosis in a time- and dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. This increase in apoptosis was associated with a decrease in Bcl-2 and expression, an increase of Bax, and an activation of caspase-3 and caspase-9. beta-lapachone treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the levels of human telomerase RNA (hTR) and c-myc expression were progressively down-regulated by beta-lapachone treatment. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of beta-lapachone.
Woo
Hyun Joo
HJ
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea.
Choi
Yung Hyun
YH
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000473:pathology*; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009285:Naphthoquinones / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D029663:Tabebuia / Q000737:chemistry; D019098:Telomerase / Q000187:drug effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009285:Naphthoquinones; D010936:Plant Extracts; D018894:Reverse Transcriptase Inhibitors; C014638:beta-lapachone; D019098:Telomerase