β-lapachone enhancement of lipid peroxidation and superoxide anion and hydrogen peroxide formation by Sarcoma 180 ascites tumor cells
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Cited by (80)
Interactions of the antioxidant enzymes NAD(P)H: Quinone oxidoreductase 1 (NQO1) and NRH: Quinone oxidoreductase 2 (NQO2) with pharmacological agents, endogenous biochemicals and environmental contaminants
2021, Chemico-Biological InteractionsCitation Excerpt :β-Lapachone is synthesized chemically from natural lapachol and exerts divergent therapeutic activities, including anticancer effect [180]. Parkinson et al. reported that β-lapachone acted as an NQO1 substrate [66] and some other studies indicated that NQO1 was involved in β-lapachone-mediated apoptosis and cytotoxicity [67–69] (Fig. 8). NQO1 competes with NADH cytochrome b5 reductase and NADPH cytochrome P450 reductase; the latter two enzymes produce one-electron reduction products (semiquinones), leading to oxidative stress [70–72].
A comprehensive review on β-lapachone: Mechanisms, structural modifications, and therapeutic potentials
2021, European Journal of Medicinal ChemistryCitation Excerpt :Besides, the antitumor effects of β-lap were also found to be related to the inhibition of a panel of enzymes, such as topoisomerase I [37], topoisomerase II [38], IDO1 [39], telomerase [40], and Hsp90 [41]. As for the mechanisms of β-lap beyond antitumor activities, such as antibacterial and trypanocidal effects [54], were also suggested to be ascribed to the rapid ROS generation triggered by NQO1 that could cause antibacterial and antitrypanosomal effects [55–57]. Moreover, the changes in the ratio between NAD+ and NADH mediated by NQO1 bioreduction were found to be associated with the therapeutic effects of β-lap on metabolic syndrome [58].
Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights
2016, European Journal of Medicinal ChemistryCitation Excerpt :While in clinical trials, β-lap (i.e., ARQ 501) has been inaccurately touted as a cell cycle checkpoint activator [13], the major determinant of cell death is through NQO1 expression [11,12a,14]. The drug is not a substrate for known multidrug resistance or drug pumps [15,16] and β-lap cell death is not affected by changes in cell cycle position, oncogenic drivers, or pro- or anti-apoptotic factors [11,12a]. Finally, the drug targets (i.e., is ‘bioactivated’ by) NQO1, a Phase II, carcinogen-inducible enzyme that is also induced by ionizing radiation (IR) in some cancer, but not normal, cells [17,18].
Photosensitizing properties of triplet furano and pyrano-1,2- naphthoquinones
2014, Journal of Photochemistry and Photobiology A: ChemistryCitation Excerpt :Naphthoquinones have been extensively studied due to their numerous biological and pharmacological activities [1–18]. The mechanism of action of these quinones is related to redox cycling, which can lead to the formation of reactive oxygen species that can damage cellular macromolecules [19–21]. β-Lapachone, a pyrano-ortho-naphthoquinone, is a natural product that is readily extracted from the heartwood of Tabebuia avellanedae, which is found mainly in South America [22–24].
NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones
2012, Biochemical PharmacologyCitation Excerpt :NQO1 catalyzes the redox cycling of β-lapachone through the generation of an unstable hydroquinone, which under aerobic conditions, is rapidly oxidized back to the parent quinone. Redox cycling of β-lapachone is characterized by the oxidation of large amounts of reduced pyridine nucleotides and the formation of reactive oxygen species including superoxide and hydrogen peroxide [78]. The reductive activation of β-lapachone by NQO1 (Fig. 3B) has been shown to result in a rapid increase in intracellular calcium leading to mitochondrial membrane depolarization, loss of ATP, DNA fragmentation and apoptosis [79,80].
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Permanent address: Instituto de Química Biológica, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina.