Suppression of Lipid Hydroperoxide-Induced Oxidative Damage to Cellular DNA by Esculetin

Kaneko, Takao; Tahara, Shoichi; Takabayashi, Fumiyo

doi:10.1248/bpb.26.840

Cited by 59 publications

(32 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The radical scavenging activity of esculetin resulted in the protection of cells from lipid peroxidation, protein carbonyl, and DNA damage induced by H 2 O 2 . The protective effects of esculetin against the increase in 8-oxodG and TBARS levels were determined after 1,1 dimethylhydrazine (DMH) administration (Kaneko et al 2003(Kaneko et al , 2007. Elevated malondialdehyde (MDA) level and decrease in superoxide dismutase (SOD) level in diabetic kidney is an indicator of increased oxidative stress (Chang et al 2005).…”

Section: Resultsmentioning

confidence: 99%

Esculetin induced changes in Mmp13 and Bmp6 gene expression and histone H3 modifications attenuate development of glomerulosclerosis in diabetic rats

Surse¹,

Gupta²,

Tikoo³

2011

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Esculetin, an antioxidant, has been used in the treatment of a variety of diseases. This study aimed to investigate the protective effect of esculetin in attenuating streptozotocin (STZ)-induced type I diabetic nephropathy and to understand the molecular mechanism involved in it. Sprague-Dawley rats were rendered diabetic using a single dose of STZ (55 mg/kg, i.p.). Protein expression of PPARg and transforming growth factor-b1 (TGF-b1) was detected by immunoblotting and immunohistochemistry respectively. RNA expression levels of Mmp13 and Bmp6 were detected by RT-PCR analysis. In diabetic rats, esculetin treatment resulted in a significant decrease in blood glucose, blood urea nitrogen, and plasma creatinine and increase in plasma albumin levels. Esculetin treatment attenuates the downregulation of PPARg in diabetic kidney, which in turn blocks the TGF-b1-mediated fibronectin expression. In addition, it attenuates the decrease in mono-methylation (K4) and acetylation of histone H3 in diabetic kidney. RT-PCR analysis revealed that esculetin treatment provides protection by decreasing antifibrotic Bmp6 and increasing fibrogenic Mmp13 mRNA expression in diabetic kidney. This is the first report to show that protection observed by esculetin treatment involves alteration in mRNA expression of Mmp13 and Bmp6 genes either directly via altered histone H3 modifications or indirectly by inhibiting the PPARg/TGF-b1 pathway.

show abstract

Section: Resultsmentioning

confidence: 99%

Esculetin induced changes in Mmp13 and Bmp6 gene expression and histone H3 modifications attenuate development of glomerulosclerosis in diabetic rats

Surse¹,

Gupta²,

Tikoo³

2011

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…17) Esculetin also scavenges hydroxyl radicals 18) and inhibits lipid peroxidation in rat liver. 19) We have previously observed that esculetin and its glycoside, esculin, suppress the formation of 8-oxodG in the DNA of cultured human diploid fibroblasts treated with linoleic acid hydroperoxide and ferric ion, 20) and that esculin is converted to esculetin in the cells. 21) Furthermore, it has been reported that esculetin inhibits mammary carcinogenesis.…”

mentioning

confidence: 99%

Inhibitory Effect of Natural Coumarin Compounds, Esculetin and Esculin, on Oxidative DNA Damage and Formation of Aberrant Crypt Foci and Tumors Induced by 1,2-Dimethylhydrazine in Rat Colons

Kaneko

Tahara

Takabayashi

2007

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Colon cancer is one of the major causes of cancer-related deaths worldwide. Oxidative stress, particularly oxidative damage to DNA, is recognized to play a role in the process of carcinogenesis.1) When cellular defense systems are overwhelmed, oxidative stress results in damage to cellular constituents including the formation of DNA adducts, peroxidation of lipids, degradation of proteins and sugars, and so on.2-4) 8-Oxo-7,8-dihydroguanine (8-oxoG) is a major oxidative DNA adduct 5) that has attracted particular attention since it is correlated with mutagenic and/or carcinogenic processes. [6][7][8] The presence of 8-oxoG residues in DNA strands leads to misreading during DNA replication, 6,9) so that the presence of 8-oxoG increases the possibility of mutagenesis. The contents of 8-oxoG or 8-oxo-2Ј-deoxyguanosine (8-oxodG), its nucleoside, have been found to be increased in target organs of animals treated with a variety of oxidative carcinogens, [10][11][12] and thiobarbituric acid reactive substances (TBARS) are widely used as a marker of in vitro lipid peroxidation. 13)Epidemiological and experimental studies suggest the strong influence of diet on colon cancer. A number of studies demonstrate the importance of natural products as chemopreventive agents.14,15) Coumarins comprise a group of natural compounds widely distributed in plants 16) that have recently attracted much attention because of their broad biological activities. Esculetin (6,7-dihydroxycoumarin) is known to be a 5-and 12-lipoxygenase inhibitor and to inhibit the production of leukotrienes and 5-hydroxyeicosatertaenoic acid through the lipoxygenase pathway.17) Esculetin also scavenges hydroxyl radicals 18) and inhibits lipid peroxidation in rat liver. 19) We have previously observed that esculetin and its glycoside, esculin, suppress the formation of 8-oxodG in the DNA of cultured human diploid fibroblasts treated with linoleic acid hydroperoxide and ferric ion, 20) and that esculin is converted to esculetin in the cells. 21) Furthermore, it has been reported that esculetin inhibits mammary carcinogenesis. 22,23) 1,2-Dimethylhydrazine (DMH) is an alkylating carcinogen that causes neoplastic changes in colonic mucosa at a level proportional to the quantity of methylated DNA adducts induced in colonic crypt cells.24) DMH-induced colon tumors are currently the most popular models in which to study the morphology, pathogenesis, prevention, and treatment of colorectal cancer.25) Aberrant crypt foci (ACF), first observed in the colonic mucosa of carcinogen-treated rodents, 26) are considered to be preneoplastic lesions, 27) since they are observed at high frequency in the colonic mucosa of patients with colon cancer 28) and rodents treated with colon carcinogens. 29)ACF can be readily identified topographically in methylene blue-stained whole colons of rodents administered carcinogenic agents, and ACF and their growth are thought to be useful indices of the effects of carcinogens and agents preventing carcinogenesis in the colon. 30) In this study, ...

show abstract

“…Qin Pi contains several pharmacologically active ingredients, including esculetin, that have in vivo anti-inflammatory and peripheral analgesic activity (11). Esculetin has been reported to suppress oxidative damage to cellular DNA induced by lipid hydroperoxide (12). Notably, esculetin has been demonstrated to suppress the proliferation of human colon cancer cells by directly targeting β-catenin (13).…”

Section: Introductionmentioning

confidence: 99%

Suppression of the Wnt signaling pathway may contribute to the inhibition of proliferation of human hepatocellular carcinoma SMMC-7721 cells by esculetin

Fan

Sun

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. The aims of the present study were to investigate the effects of esculetin on the proliferation of human hepatocellular carcinoma SMMC-7721 cells and to determine the underlying mechanism behind this activity. An MTT assay was used to assess cell proliferation, reverse transcription-quantitative polymerase chain reaction was used to determine the relative mRNA expression levels of β-catenin, c-Myc and cyclin D1, and western blot analysis was utilized to determine the levels of the associated proteins. Compared with the dimethyl sulfoxide control, esculetin reduced the cell viability of SMMC-7721 and HL-7702 cells in a dose-and time-dependent manner. Treatment of SMMC-7721 cells with esculetin resulted in downregulation of the mRNA and protein levels of β-catenin, c-Myc and cyclin D1. Esculetin increased the phosphorylation of β-catenin at Ser33/Ser37/Thr41 and inhibited the proliferation of human hepatoma SMMC-7721 cells by suppressing the Wnt signaling pathway. The results of the present study suggest that esculetin inhibited the Wnt/β-catenin signaling pathway in SMMC-7721 cells and may have potential as an effective anti-cancer drug, acting to inhibit the Wnt/β-catenin signaling pathway.

show abstract

Suppression of Lipid Hydroperoxide-Induced Oxidative Damage to Cellular DNA by Esculetin

Cited by 59 publications

References 26 publications

Esculetin induced changes in Mmp13 and Bmp6 gene expression and histone H3 modifications attenuate development of glomerulosclerosis in diabetic rats

Esculetin induced changes in Mmp13 and Bmp6 gene expression and histone H3 modifications attenuate development of glomerulosclerosis in diabetic rats

Inhibitory Effect of Natural Coumarin Compounds, Esculetin and Esculin, on Oxidative DNA Damage and Formation of Aberrant Crypt Foci and Tumors Induced by 1,2-Dimethylhydrazine in Rat Colons

Suppression of the Wnt signaling pathway may contribute to the inhibition of proliferation of human hepatocellular carcinoma SMMC-7721 cells by esculetin

Contact Info

Product

Resources

About