ß-Lapachone | Topoisomerase-1 inhibitor

β-Lapachone (4707-32-8) is a naturally occurring quinone found in the bark of the Lapacho tree (Tabebuia avellanedae). A novel DNA topoisomerase I inhibitor which unlike camptothecin does not stabilize the cleavable complex indicating a novel mode of action.¹ Induces apoptosis in a number of cancer cell lines.² In cancer cells over-expressing NAD(P)H:quinone oxidoreductase, reduction of β-lapachone leads to futile cycling between quinone and hydroquinone forms³ resulting in the production of reactive oxygen species⁴. Suppresses radiation-induced activation of NFκB.⁵

References/Citations:

1) Li et al. (1993), beta-Lapachone, a Novel DNA Topoisomerase I Inhibitor With a Mode of Action Different From Camptothecin; J. Biol. Chem., 268 22463
2) Wuerzberger et al. (1998), Induction of Apoptosis in MCF-7:WS8 Breast Cancer Cells by Beta-Lapachone; Cancer Res., 58 1876
3) Pink et al. (2000), NAD(P)H:Quinone Oxidoreductase Activity Is the Principal Determinant of Beta-Lapachone Cytotoxicity. J. Biol. Chem., 275 5416
4) Siegel et al. (2012), NAD(P)H:quinone Oxidoreductase 1 (NQO1) in the Sensitivity and Resistance to Antitumor Quinones; Biochem. Pharmacol., 83 1033
5) Dong et al. (2010), Beta-lapachone suppresses radiation-induced activation of nuclear factor-kappaB; Exp. Mol. Med., 42 327