2007
DOI: 10.1016/j.freeradbiomed.2007.03.035
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Abstract: Altered redox signaling and regulation in cancer cells represent a chemical vulnerability that can be targeted by selective chemotherapeutic intervention. Here, we demonstrate that 3,7-diaminophenothiazinium-based redoxcyclers (PRC) induce selective cancer cell apoptosis by NAD (P)H:quinone oxidoreductase (NQO1)-dependent bioreductive generation of cellular oxidative stress. Using PRC lead compounds including toluidine blue against human metastatic G361 melanoma cells, apoptosis occurred with phosphatidylserin… Show more

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Cited by 53 publications
(88 citation statements)
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References 52 publications
(65 reference statements)
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“…We have previously observed a pronounced increase in the expression of the P. aeruginosa class II RNR gene and impaired dNTP synthesis caused by hydroxyurea treatment (33). The increased RNR gene expression in conjunction with depletion of dNTP levels indicates that RNR is targeted by toluidine blue and streptonigrin, thus suggesting a novel activity for these compounds that may be as relevant as their previously reported effects (26)(27)(28)(29)(30)(31)(32). Our results suggest that inhibition of growth is attributable to impaired DNA synthesis as a result of low dNTP pools.…”
Section: Discussionmentioning
confidence: 78%
See 1 more Smart Citation
“…We have previously observed a pronounced increase in the expression of the P. aeruginosa class II RNR gene and impaired dNTP synthesis caused by hydroxyurea treatment (33). The increased RNR gene expression in conjunction with depletion of dNTP levels indicates that RNR is targeted by toluidine blue and streptonigrin, thus suggesting a novel activity for these compounds that may be as relevant as their previously reported effects (26)(27)(28)(29)(30)(31)(32). Our results suggest that inhibition of growth is attributable to impaired DNA synthesis as a result of low dNTP pools.…”
Section: Discussionmentioning
confidence: 78%
“…Both are dyes with various uses in histology, for example, and are capable of two-electron redox cycling under physiological conditions (25). They induce cancer cell apoptosis and have activity against some bacteria (26,27). The extreme IC 50 of toluidine blue, below the enzyme concentration in the assay, excludes pure competitive inhibition and instead indicates that its activity is redox-related.…”
Section: Discussionmentioning
confidence: 99%
“…Flow Cytometric Detection of Cleaved Procaspase-3-Treatment-induced proteolytic caspase-3 activation was examined using an antibody directed against cleaved/activated caspase-3 (Asp-175) (Alexa Fluor 488 conjugate; Cell Signaling) followed by flow cytometric analysis as published (45,46).…”
Section: Methodsmentioning
confidence: 99%
“…Detection of Intracellular Oxidative Stress by Flow Cytometric Analysis-Induction of intracellular oxidative stress by test compound was analyzed by flow cytometry using 2Ј,7Ј-dichlorodihydrofluorescein diacetate (DCFH-DA) as a sensitive nonfluorescent precursor dye according to a published standard procedure (46).…”
Section: Methodsmentioning
confidence: 99%
“…Photodynamic induction of intracellular oxidative stress and its suppression by Nrf2-activators was analyzed by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) as a sensitive non-fluorescent precursor dye according to a published standard procedure [45,49]. Human Hs27 skin fibroblasts were pretreated with test compounds for 24 h and then exposed to singlet oxygen generated by dye-sensitization as described above (visible light dose 0.3 J/cm 2 ), followed by DCFH-DA loading.…”
Section: Detection Of Intracellular Oxidative Stress By Flow Cytometrmentioning
confidence: 99%