Beta-lapachone (LAPA) decreases cell viability and telomerase activity in leukemia cells: suppression of telomerase activity by LAPA.
Up-regulation of telomerase activity is associated with immortalization and unlimited cell division in most cancer cells. Therefore, telomerase represents a particularly attractive target for anticancer therapy. Recent reports have suggested that beta-lapachone (LAPA), the product of the South American Tabebuia avellanedae tree, inhibits growth of tumor cells. However, the underlying relationship between telomerase activity and apoptosis in response to LAPA exposure in leukemia cells remains poorly understood. In this study, we confirmed that LAPA treatment induces direct cytotoxicity in human leukemia cells (U937, K562, HL60, and THP-1) through activation of caspase-3 and subsequent cleavage of poly(ADP-ribose) polymerase. The observed induction of cell death was associated with decreased telomerase activity, which was ascribed to down-regulation of telomerase reverse transcriptase. Additionally, overexpression of anti-apoptotic Bcl-2 could not overcome the induction of apoptosis or the decreased telomerase activity in response to treatment of U937 cells with LAPA. We conclude that LAPA has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells.
Moon
Dong-Oh
DO
Department of Marine Sciences, Jeju National University, Jeju, Republic of Korea.
Kang
Chang-Hee
CH
Kim
Mun-Ock
MO
Jeon
You-Jin
YJ
Lee
Jae-Dong
JD
Choi
Yung Hyun
YH
Kim
Gi-Young
GY
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology*; D009285:Naphthoquinones / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D029663:Tabebuia / Q000737:chemistry; D019098:Telomerase / Q000378:metabolism*; D020298:U937 Cells
D009285:Naphthoquinones; D010936:Plant Extracts; C014638:beta-lapachone; D011065:Poly(ADP-ribose) Polymerases; D019098:Telomerase; D053148:Caspase 3