Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

doi:10.1016/j.tox.2011.01.020

Cited by 27 publications

(13 citation statements)

References 43 publications

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“…This action further facilitated subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFαsignaling, which contributed to tumor promotion. In rat tissue, EMIQ reduces proinflammatory proteins (TNFα) expression and cell cycle regulation molecules (Cdc20 and Cdkn2b) [87] . Enzymatically modified IQ suppressed the liver tumorpromoting activity of phenobarbital by inhibiting nuclear translocation of constitutive active/androstane receptor (CAR), and not by suppressing oxidative stress in rats.…”

Section: Liver Cancermentioning

confidence: 99%

“…Outside the GSTP(+) foci, IQ suppresses apoptosis of nontransformed liver cells [90] . In addition, other possible signaling interactions of IQ could involve changes in the reduction of proinflammatory proteins such as TNFα and other cytokines such as TGFβ [87] . It is evident that numerous mechanisms are possible mediators of the actions of IQ.…”

Section: Antitumor Mechanisms Of Iqmentioning

confidence: 99%

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Review of anticancer mechanisms of isoquercitin

Orfali¹,

Duarte²,

Bonadio³

et al. 2016

WJCO

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This review was based on a literature search of PubMed and Scielo databases using the keywords "quercetin, rutin, isoquercitrin, isoquercitin (IQ), quercetin-3-glucoside, bioavailability, flavonols and favonoids, and cancer" and combinations of all the words. We collected relevant scientific publications from 1990 to 2015 about the absorption, bioavailability, chemoprevention activity, and treatment effects as well as the underlying anticancer mechanisms of isoquercitin. Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom. The subclass of flavonols receives special attention owing to their health benefits. The main components of this class are quercetin, rutin, and IQ, which is a flavonoid and although mostly found as a glycoside, is an aglycone (lacks a glycoside side chain). This compound presents similar therapeutic profiles to quercetin but with superior bioavailability, resulting in increased efficacy compared to the aglycone form. IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant, antiproliferative, anti-inflammatory, anti-hypertensive, and anti-diabetic. The protective effects of IQ in cancer may be due to actions on lipid peroxidation. In addition, the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway, mixed-lineage protein kinase 3, mitogen-activated protein kinase, apoptotic pathways, as well proinflammatory protein signaling. This review contributed to clarifying the mechanisms of absorption, metabolism, and actions of IQ and isoquercitrin in cancer.

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Section: Liver Cancermentioning

confidence: 99%

Section: Antitumor Mechanisms Of Iqmentioning

confidence: 99%

Review of anticancer mechanisms of isoquercitin

Orfali¹,

Duarte²,

Bonadio³

et al. 2016

WJCO

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“…It has been demonstrated in our previous studies that COX-2 is related to the liver tumor promoting effect of BNF (Shimada et al, 2010;Kuwata et al, 2011). COX-2 may be involved in the early stage of hepatocarcinogenesis, and the increased expression of COX-2 in noncancerous liver tissues has been significantly associated with shorter disease-free survival in patients with hepatocellular carcinomas (Cervello and Montalto, 2006).…”

Section: Discussionmentioning

confidence: 82%

Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone

et al. 2012

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-Omeprazole (OPZ) and β-naphthoflavone (BNF) are cytochrome P450 (CYP)1A inducers and have liver tumor promoting effects. In this study, we investigated the co-promoting and co-initiating effects of OPZ and BNF in rats. In Experiment 1, male rats were subjected to partial hepatectomy (PH), and given oral doses of 138 or 276 mg/kg OPZ, 0.125% or 0.25% BNF or 138 mg/kg OPZ+0.125% BNF (n = 9~12) for 6 weeks after N-diethylnitrosamine (DEN) initiation. In Experiment 2, male rats were treated with oral doses of 138 or 276 mg/kg OPZ, 0.03% or 0.06% BNF or 138 mg/kg OPZ+0.03% BNF (n = 11~12) for 9 days starting 1 week before initiating treatment. As an initiating treatment, 2-Amino-3,4-dimethylimidazo[4,5-f]quinolone (MeIQx) was orally administered 12 hr after PH. The rats were fed a basal diet for 15 days, followed by a diet containing 0.015% 2-acetylaminofluorene for the next 10 days with a single oral dose of carbon tetrachloride. In Experiment 1, the number and area of glutathione S-transferase placental form-positive foci in the OPZ+BNF group were significantly higher than the average values of the High OPZ or the High BNF group. The expression of cyclooxygenase-2 (Cox-2) and COX-2 protein in the liver significantly increased in the OPZ+BNF group. In Experiment 2, liver initiation activity was not enhanced by the co-administration of OPZ+BNF. The results of our studies suggest that the co-administration of OPZ and BNF results in synergistic effects in the liver tumor promotion probably owing to increased COX-2 expression, but no modifying effect in the liver initiation activity of MeIQx in rats.

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“…In the present study, mean postweaning exposure level of exogenously administered AGIQ or ALA in PTU-exposed offspring was 516.1 and 103.4 mg/kg body weight/ day, respectively. While antioxidant effect of AGIQ has not been reported in the brain injury model until now, 5,000 ppm dietary dose of AGIQ has shown to suppress hepatocellular tumor promotion in rats (Fujii et al, 2013a;Hara et al, 2014;Kuwata et al, 2011). These Table 2.…”

Section: Discussionmentioning

confidence: 97%

“…Both AGIQ and ALA were powdered compound and mixed with powdered basal diet to the determined concentration. The chosen dosage of AGIQ or ALA has been shown to suppress the promotion of hepatic preneoplastic lesions in rats (Fujii et al, 2013a(Fujii et al, , 2013bHara et al, 2014;Kuwata et al, 2011). All dams of PTU-exposed group were euthanized on PND 28.…”

Section: Experimental Designmentioning

confidence: 99%

Ameliorating effect of postweaning exposure to antioxidant on disruption of hippocampal neurogenesis induced by developmental hypothyroidism in rats

et al. 2019

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Developmental hypothyroidism as a model of autism spectrum disorders disrupts hippocampal neurogenesis through the adult stage. The present study investigated the ameliorating effect of postweaning exposure to antioxidant on the hypothyroidism-induced disruptive neurogenesis. Mated female Sprague-Dawley rats were treated with 0 or 10 ppm 6-propyl-2-thiouracil (PTU) as an anti-thyroid agent in drinking water from gestational day 6 to postnatal day (PND) 21 on weaning. PTU-exposed male offspring were fed either basal diet, diet containing α-glycosyl isoquercitrin (AGIQ) at 5,000 ppm or α-lipoic acid (ALA) at 1,000 ppm as an antioxidant from PND 21 to PND 77. PTU-exposure decreased DCX + and NeuN + granule cell lineage subpopulations, synaptic plasticity-related FOS + granule cells, and hilar PVALB + and GAD67 + GABAergic interneurons, increased hilar SST + and CALB2 + interneurons, and upregulated Gria3, Otx2, and antioxidant enzyme genes in the dentate gyrus on PND 77. These results suggest disruption of neurogenesis remained in relation with increase of oxidative stress and compensatory responses to the disruption at the adult stage. AGIQ recovered expression of some antioxidant enzyme genes and was effective for restoration of NeuN + postmitotic granule cells and PVALB + and SST + interneurons. In contrast, ALA was effective for restoration of all interneuron subpopulations, as well as postmitotic granule cells, and upregulated Grin2a that may play a role for the restoration. Both antioxidants recovered expression of Otx2 and AGIQ-alone recovered Gria3, suggesting a reversal of disruptive neurogenesis by compensatory responses. Thus, postweaning antioxidant exposure may be effective for ameliorating developmental hypothyroidism-induced disruptive neurogenesis by restoring the function of regulatory system.

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Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

Cited by 27 publications

References 43 publications

Review of anticancer mechanisms of isoquercitin

Review of anticancer mechanisms of isoquercitin

Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone

Ameliorating effect of postweaning exposure to antioxidant on disruption of hippocampal neurogenesis induced by developmental hypothyroidism in rats

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