Morphologic Analysis Correlates with Gene Expression Changes in Cultured F344 Rat Mesothelial Cells

Crosby, Lynn M.; Hyder, Karim; DeAngelo, Anthony B.; Kepler, Thomas B.; Gaskill, Betty; Benavides, Gina; Yoon, Lawrence; Morgan, Kevin T.

doi:10.1006/taap.2000.9049

Cited by 60 publications

(60 citation statements)

References 36 publications

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“…It has been reported that oxidative stress induces activation of transcription factors and the expression of several oncogenes, including AP-1, NF-κB, c-myc, and c-fos, which enhance cell proliferation (37). Reducing oxidative stress may suppress the proliferation of tumor cells (38). The results of the current study demonstrate that quercitrin can act as an antioxidant as well as ascorbic acid, over the same concentration range in vitro.…”

Section: Discussionsupporting

confidence: 58%

Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin

Ding¹

2009

Int J Oncol

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Abstract. Quercitrin, glycosylated form of flavonoid compounds, is widely distributed in nature. Extensive studies have demonstrated that quercitrin exhibits strong antioxidant and anti-carcinogenic activities. However, the molecular mechanism is poorly understood. The present study examines the effects of quercitrin on tumor promotion in mouse JB6 cells, a validated model for screening cancer chemopreventive agents and elucidating the molecular mechanisms. Quercitrin blocked TPA-induced neoplastic transformation in JB6 P + cells. Pretreatment of JB6 cells with quercitrin down-regulated transactivation of AP-1 and NF-κB induced by UVB or TPA. In the skin of AP-1-luciferase transgenic mice, topical treatment of the mouse with quercitrin markedly blocked the TPA-induced AP-1 transactivation. Further studies indicated that these inhibitory actions appear to be mediated through the inhibition of MAPKs phosphorylation, including ERKs, p38 kinase, and JNKs. In addition, quercitrin stimulated the activation of NF-E2-related factor (Nrf2) and GST AREluciferase activity. Comet assays showed that quercitrin could block DNA damage induced by UVB. To our knowledge, these results provide the first evidence that quercitrin contributes to the inhibition of neoplastic transformation by blocking activation of the MAPK pathway and stimulation of cellular protection signaling. Moreover, to our knowledge, these findings provide the first molecular basis for the anticarcinogenic action of quercitrin. IntroductionPrevious studies have indicated that reactive oxidative species (ROS) function as second messengers in numerous signaling pathways involved in a diverse array of biological responses ranging from transcriptional regulation, differentiation and proliferation to oncogenic transformation (1,2). Increased formation of ROS can promote the development of malignancy, and the 'normal' rates of ROS generation may account for the increased risk of cancer development and neurodegenerative disorders (3,4). Therefore, interventions favoring the scavenging of ROS (dietary and pharmacological antioxidants) to attenuate the oxidative stress may prevent oxidant stressassociated diseases. A report published by the American Institute for Cancer Research regarding dietary prevention of cancer indicates that 7-31% of all cancers worldwide could be reduced by diets high in fruits and vegetables (5). Thus, searching for novel natural agents and defining novel targets for chemoprevention have become an important area of investigation.Flavonoids are components of the human diet and are widely found in vegetables and fruits (4). Flavonoids exert various biological activities, which are mainly related to their abilities to inhibit enzymes, to their antioxidant properties, and to their effects on immune responses (6). These activities may explain the beneficial effects that flavonoid intake exerts in different human pathologies, including hypertension, inflammatory conditions, and cancer (7). Quercetin is the most abundant bioflavonoid compound, which ...

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Section: Discussionsupporting

confidence: 58%

Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin

Ding¹

2009

Int J Oncol

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“…It has been reported that oxidative stress induces the expression of several oncogenes, such as c-myc and c-fos, which enhance cell proliferation (45,46). Compared with nonneoplastic cells, cancer cells constitutively generate large but nonlethal amounts of ROS that apparently function as signaling molecules in the MAPK pathway to constantly activate redox-sensitive transcription factors and responsive genes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Activator Protein-1, NF-κB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid

Feng¹,

Bowman

et al. 2005

Journal of Biological Chemistry

356

241

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“…DNA damage due to oxidative stress in the livers of mice exposed to halogenated acetic acids, including DBA (Austin et al, 1996), may also contribute to the hepatocarcinogenicity of these chemicals. A study of gene expression in immortalized rat peritoneal mesothelial cells incubated with potassium bromate detected increases in oxidative stress responsive genes, as well as changes in genes that regulate DNA repair and cell cycling (Crosby et al, 2000a). The carcinogenicity of DBA may involve a genotoxic mechanism since this chemical induces DNA damage in E. coli (Giller et al, 1997), mutations in Salmonella typhimurium strain TA98 and TA100 with and without metabolic activation , and DNA strand breaks in Chinese hamster ovary cells .…”

Section: Discussionmentioning

confidence: 99%

Toxicity and carcinogenicity of the water disinfection byproduct, dibromoacetic acid, in rats and mice

et al. 2007

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Dibromoacetic acid (DBA) is a water disinfection byproduct formed by the reaction of chlorine oxidizing compounds with natural organic matter in water containing bromide. Male and female F344/N rats and B6C3F 1 mice were exposed to DBA in drinking water for 2 weeks (N=5), 3 months (N=10), or 2 years (N=50). Concentrations of DBA in drinking water were 0, 125, 250, 500, 1,000, and 2,000 mg/L in the 2-week and 3-month studies, and 0, 50, 500, and 1,000 mg/L in the 2-year studies. Toxic effects of DBA in the prechronic studies were detected in the liver (hepatocellular cytoplasmic vacuolization in rats and mice) and testes (delayed spermiation and atypical residual bodies in male rats and mice, and atrophy of the germinal epithelium in rats). In the 2-year studies, neoplasms were induced at multiple sites in rats and mice exposed to DBA; these included mononuclear cell leukemia and abdominal cavity mesothliomas in rats, and neoplasms of the liver (hepatocellular adenoma or carcinoma and hepatoblastoma) and lung (alveolar adenoma or carcinoma) in mice. The increase in incidence of hepatocellular neoplasms in male mice was significant even at the lowest exposure concentration of 50 mg/L, which is equivalent to an average daily dose of approximately 5 mg/kg. These studies provide critical information for future reevaluations of health-based drinking water standards for haloacetic acids.

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Morphologic Analysis Correlates with Gene Expression Changes in Cultured F344 Rat Mesothelial Cells

Cited by 60 publications

References 36 publications

Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin

Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin

Inhibition of Activator Protein-1, NF-κB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid

Toxicity and carcinogenicity of the water disinfection byproduct, dibromoacetic acid, in rats and mice

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