The Chemopreventive Capacity of Quercetin to Induce Programmed Cell Death in Hepatocarcinogenesis

Vásquez-Garzón, Verónica Rocío; Macías‐Pérez, José Roberto; Jiménez-García, Mónica Noemí; Villegas, Vanessa; Fattel-Fazenta, Samia; Villa‐Treviño, Saúl

doi:10.1177/0192623312467522

Cited by 21 publications

(16 citation statements)

References 35 publications

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“…This model has been used by us [9] and other authors in order to observe the three different stages associated with the development of HCC: initiation, promotion, and progression [11, 16, 17]. The evaluation of the presence of preneoplastic lesions was done through the activity of the GGT.…”

Section: Discussionmentioning

confidence: 99%

“…We have also previously reported that quercetin has a chemopreventive effect on the liver of rats when this is used previously to the use of the MRHM to induce HCC. Quercetin reduces the number of cells initiated to cancer through decreasing lipoperoxidation, activating caspases 3 and 9, and promoting the enzymatic and nonenzymatic antioxidant defense system during the initiation of hepatocarcinogenesis [8, 9]. While the use of chemoprotective substances would have a major impact on the incidence of HCC, it is also necessary to discover substances that contribute to reverse the injuries, since this type of cancer is usually detected in late stages.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the detection of gamma-glutamyl transpeptidase (GGT) is a useful tool, which has been used in detecting HCC-related lesions. GGT is not present in hepatocytes of adult rats, but it is detected in altered hepatic foci induced by carcinogens, in most animal models, from the initial lesions caused by carcinogens until the tumor formation [9]. …”

Section: Introductionmentioning

confidence: 99%

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Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

Torres

Monroy-Ramírez

Martínez-Guerra

et al. 2017

Oxidative Medicine and Cellular Longevity

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Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

Torres

Monroy-Ramírez

Martínez-Guerra

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Hepatocellular carcinoma (HCC) is sixth commonly prevalent cancers and ranks third in causing mortality worldwide (Vasquez‐Garzon et al, ). Though the majority of HCC cases are detected in the developing countries of Asia and Africa and results in >1 million deaths across the globe.…”

Section: Introductionmentioning

confidence: 99%

Acteoside‐mediates chemoprevention of experimental liver carcinogenesis through STAT‐3 regulated oxidative stress and apoptosis

Peerzada

Faridi

Sharma

et al. 2016

Environmental Toxicology

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In the absence of an effective therapy against Hepatocellular Carcinoma (HCC), chemoprevention remains an important strategy to circumvent morbidity and mortality. Here, we examined chemopreventive potential of Acteoside (ACT), a plant derived phenylethanoid glycoside against an environmental and dietary carcinogen, diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. ACT treatment (0.1 and 0.3% supplemented with diet) started 2 weeks before DEN challenge and continued for 18 weeks thereafter, showed a remarkable chemopreventive activity. ACT treatment resulted in reduced HCC nodules. Histopathology showed progressive tissue damage, necrosis (5 weeks), hepatocytic injury (10 weeks), anisonucleosis with presence of prominent nucleoli, sinusidal dilations, and lymphomono nuclear inflammation (18 weeks). Biochemical analysis showed hepatocytic injury (raised ALT, p < 0.001), inflammation [IL-6, IFN-γ (p < 0.05), and TNF-α (p < 0.001)], apoptosis [elevated Caspase-3 (p < 0.001)]. ACT at 0.1 and 0.3% ameliorated DEN-induced pre-hepatocarcinogenic manifestations. Mechanistic studies of ACT chemoprevention was elucidated using Hep3B cells with an aim to develop an in vitro DEN-induced toxicity model. Hep3B was found to be a reliable and more sensitive towards DEN toxicity compared to HepG2 and HuH7 cells. ACT prevented DEN-induced cytotoxicity (p < 0.001), DNA damage, and genotoxicity (micronuclei test, DNA ladder test, Hoechst staining, cell cycle analysis). ACT significantly (p < 0.001) scavenged DEN-induced reactive oxygen species (ROS) levels and prevented mitochondrial membrane potential (MMP) loss. Immunoblotting showed ACT treatment reversed DEN-induced NF-κB, Bax, Cytochrome C, Bcl-2, and Stat-3 levels. We conclude that chemoprotective effect of ACT is mediated by STAT-3 dependent regulation of oxidative stress and apoptosis and ACT has potential to be developed as a chemopreventive agent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 782-798, 2016.

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“…Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities [1] .Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin [2] .Quercetin (3,3',4',5,7-pentahydroxy flavone, quercetin) is a grown-derived flavonoids, widely found in herbal and food [3][4][5] . Quercetin displays antioxidant, anti-inflammatory, anti-metastatic and anticancer activities [6][7][8][9][10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of the novel Antioxidant Agent Quercetin Derivatives

Qu¹,

Zhao²,

Wu³

et al. 2015

Proceedings of the 3rd International Conference on Material, Mechanical and Manufacturing Engineering

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Three 3-substituted derivatives of quercetin were synthesized in 10-80% overall yields. Their structures were characterized by 1 HNMR. Three target compounds (4a~4c) have not been reported before. The results showed that: pre-treated of PC-12 cells with, cell survival rate was higher than that of quercetin. In this project, the oxidative damage model of PC-12 cells was established and the antioxidant activities of three newly synthesized quercetin derivatives were evaluated. Among them, compound 4b (30μM) showed the highest antioxidant activity against H 2 O 2. Cell viability in pre-treated with or without compound 4b (30μM) were 53.05% and 10.31%, higher than that of quercetin (47.22%).

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The Chemopreventive Capacity of Quercetin to Induce Programmed Cell Death in Hepatocarcinogenesis

Cited by 21 publications

References 35 publications

Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

Acteoside‐mediates chemoprevention of experimental liver carcinogenesis through STAT‐3 regulated oxidative stress and apoptosis

Synthesis and Biological Evaluation of the novel Antioxidant Agent Quercetin Derivatives

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