Induction of NQO1 in Cancer Cells

Begleiter, Asher; Fourie, Jeanne

doi:10.1016/s0076-6879(04)82018-4

Cited by 46 publications

(35 citation statements)

References 83 publications

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“…A higher frequency of G to T transversion has been documented in animals exposed to PAH carcinogens (37). The enhanced activities of phase I and II enzymes as well as increased expression of 8-OH-dG seen in HBP tumours in the present study corroborate overexpression of these enzymes and oxidative DNA damage reported in cell lines and malignant tumours (26,38,39).…”

Section: Biochemical Findingssupporting

confidence: 88%

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

et al. 2008

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Objective-To evaluate the chemopreventive potential of the black tea polyphenols Polyphenon-B and BTF-35 during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.Design-Hamsters were divided into 6 groups. Groups 2 and 3 animals received diet containing Polyphenon-B and BTF-35 respectively, four weeks before carcinogen administration when they were 6 weeks of age and continued until the final exposure to carcinogen. At 10 weeks of age, animals in groups 1, 2 and 3 were painted with 0.5% DMBA 3 times a week for 14 weeks. Groups 4 and 5 animals were given Polyphenon-B and BTF-35 alone respectively as in groups 2 and 3. Animals in group 6 served as control. All the animals were sacrificed after an experimental period of 18 weeks. Phase I and phase II xenobiotic-metabolizing enzymes and 8-hydroxy deoxyguanosine (8-OH dG) in the buccal pouch and liver were used as biomarkers of chemoprevention.Results-Hamsters painted with DMBA showed increased expression of 8-OH-dG and enhanced activities of phase I (CYP450; total as well as CYP1A1, 1A2 and 2B isoforms and cytochrome b 5 ) and phase II (GST and quinone reductase) xenobiotic-metabolizing enzymes with increased immunohistochemical expression of CYP1A1, and CYP1B1 isoforms in the buccal pouch. This was accompanied by increased phase I and decreased phase II enzyme activities in the liver. Administration of Polyphenon-B and BTF-35 significantly decreased tumour incidence, oxidative DNA damage, phase I enzyme activities as well as expression of CYP1A1 and CYP1B1 isoforms, while enhancing phase II enzyme activities in the buccal pouch and liver.Conclusion-Our results provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. Furthermore, the greater efficacy of BTF-35 in chemoprevention of HBP carcinomas via inhibition of oxidative DNA damage and modulation of xenobiotic-metabolizing enzymes may have a major impact in human oral cancer prevention.

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Section: Biochemical Findingssupporting

confidence: 88%

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

et al. 2008

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“…In numerous animal and cell culture models, NQO1 is elevated/ induced in normal tissues/cells in response to low-level carcinogen (22) or ionizing radiation (23) exposures. Importantly, levels of this two-electron oxidoreductase are commonly endogenously elevated 2-to 30-fold in many tumors, including NSCLCs, vs. most human normal tissues (8,16,24).…”

Section: Discussionmentioning

confidence: 99%

An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by β-lapachone

Bey

Bentle²,

Reinicke

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

332

381

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Lung cancer is the number one cause of cancer-related deaths in the world. Patients treated with current chemotherapies for non-smallcell lung cancers (NSCLCs) have a survival rate of Ϸ15% after 5 years. Novel approaches are needed to treat this disease. We show elevated NAD(P)H:quinone oxidoreductase-1 (NQO1) levels in tumors from NSCLC patients. ␤-Lapachone, an effective chemotherapeutic and radiosensitizing agent, selectively killed NSCLC cells that expressed high levels of NQO1. Isogenic H596 NSCLC cells that lacked or expressed NQO1 along with A549 NSCLC cells treated with or without dicoumarol, were used to elucidate the mechanism of action and optimal therapeutic window of ␤-lapachone. NSCLC cells were killed in an NQO1-dependent manner by ␤-lapachone (LD 50, Ϸ4 M) with a minimum 2-h exposure. Kinetically, ␤-lapachone-induced cell death was characterized by the following: (i) dramatic reactive oxygen species (ROS) formation, eliciting extensive DNA damage; (ii) hyperactivation of poly(ADP-ribose)polymerase-1 (PARP-1); (iii) depletion of NAD ؉ /ATP levels; and (iv) proteolytic cleavage of p53/PARP-1, indicating -calpain activation and apoptosis. ␤-Lapachone-induced PARP-1 hyperactivation, nucleotide depletion, and apoptosis were blocked by 3-aminobenzamide, a PARP-1 inhibitor, and 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester (BAPTA-AM), a Ca 2؉ chelator. NQO1 ؊ cells (H596, IMR-90) or dicoumarol-exposed NQO1 ؉ A549 cells were resistant (LD50, >40 M) to ROS formation and all cytotoxic effects of ␤-lapachone. Our data indicate that the most efficacious strategy using ␤-lapachone in chemotherapy was to deliver the drug in short pulses, greatly reducing cytotoxicity to NQO1 ؊ ''normal'' cells. ␤-Lapachone killed cells in a tumorselective manner and is indicated for use against NQO1 ؉ NSCLC cancers.DNA repair inhibitor ͉ non-small-cell lung cancer ͉ NQO1 ͉ apoptosis ͉ -calpain cell death

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“…Thus, with most quinones, their conversion to the relatively redox-stable hydroquinones by NQO1 is regarded as a detoxification process (1, 3, 5 -7, 10). In fact, the chemopreventive activity of a variety of synthetic compounds and vegetables and fruits have been attributed to their ability to up-regulate NQO1 and other phase II detoxifying enzymes in cells (1).…”

mentioning

confidence: 99%

Heat-Induced Up-Regulation of NAD(P)H:Quinone Oxidoreductase Potentiates Anticancer Effects of β-Lapachone

Park

Choi

et al. 2005

Clinical Cancer Research

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Purpose: The purpose of the present study was to evaluate the efficacy of mild hyperthermia to potentiate the anticancer effects of h-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) by up-regulating NAD(P)H:quinone oxidoreductase (NQO1) in cancer cells. Experimental Design: Effects of h-lapachone alone or in combination with mild heating on the clonogenic survival of FSaII fibrosarcoma cells of C3H mice and A549 human lung tumor cells in vitro was determined. Effects of heating on the NQO1 level in the cancer cells in vitro were assessed using Western blot analysis for NQO1 expression, biochemical determination of NQO1 activity, and immunofluorescence microscopy for NQO1 expression. Growth of FSaII tumors in the hind legs of C3H mice was determined after treating the host mice with i.p. injection of 45 mg/kg h-lapachone followed by heating the tumors at 42jC for 1 hour every other day for four times.

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Induction of NQO1 in Cancer Cells

Cited by 46 publications

References 83 publications

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by β-lapachone

Heat-Induced Up-Regulation of NAD(P)H:Quinone Oxidoreductase Potentiates Anticancer Effects of β-Lapachone

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