Cancer Prevention Mediated by Caffeic Acid Phenethyl Ester Involves Cyp2b1/2 Modulation in Hepatocarcinogenesis

Beltrán-Ramírez, Olga; Pérez, Roberto Macías; Sierra-Santoyo, Adolfo; Villa‐Treviño, Saúl

doi:10.1177/0192623311431947

Cited by 15 publications

(7 citation statements)

References 27 publications

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“…For example, this model has been used to demonstrate the chemopreventive effect of folic acid on preneoplastic lesions (35). Similar effects have been observed when applying caffeic acid phenethyl ester (36) and ethanol ethanol extract of Phellinus merrillii (37).…”

Section: Discussionsupporting

confidence: 69%

Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver

et al. 2019

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Matrine (C15H24N2O) is an alkaloid extracted from the Chinese herb Sophora flavescens that has anti-fibrotic and anti-cancer properties. The aim of the present study was to determine the chemopreventive effect of matrine on the development of primary hepatocellular carcinoma (HCC) and its possible association with the suppression of the Notch signaling pathway. The rats were randomly divided into four groups: Control, model, low-dose matrine and high-dose matrine groups. The model was established by combining a partial hepatectomy with diethylnitrosamine (DEN) + 2-acetylaminofluorene (2-AAF). Low-and high-dose matrine groups received intragastric administration of matrine (0.25 and 2.5 g/l of matrine, respectively). DEN + 2-AAF injections and hepatectomy were not performed in the control group. All rats were sacrificed 2, 4 and 7 weeks after hepatectomy. HCC-like histopathological lesions were detected using hematoxylin and eosin staining. The expression levels of α-1-fetoprotein (AFP), albumin (ALB), Notch1 and Hes1 were analyzed using immunohistochemistry. Hepatic lobule structure loss, liver tissue necrosis and inflammatory cell infiltration, and edema degeneration were observed in the model group. By contrast, hepatocyte cord structure was restored and hepatocyte edema degeneration was significantly reduced after 7 weeks of treatment with matrine. In addition, compared with the model group, matrine reduced the expression of AFP, increased the expression of ALB and reduced the expression of Notch1 and Hes1 (only for high-dose matrine; all P<0.05). The findings suggested that matrine could prevent the early development of HCC-like lesions in a rat model, possibly by modulating Notch pathway activation.

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Section: Discussionsupporting

confidence: 69%

Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver

et al. 2019

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“…Moreover, chrysin, is an effective inhibitor of midazolam 4-hydroxylase in HLMs ( 18 ). Also CAPE, one of the major biologically active components of propolis, had CYP1A2 inhibitory activity in HLM ( 19 ) and diminished hepatic protein levels of CYP1A2 and CYP2B1/2 in rats ( 20 ). Also, CAPE inhibits 3-methylcholanthrene-induced CYP1A1 expression through induction of hypoxia-inducible factor-1 ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cytochrome P450 by Propolis in Human Liver Microsomes

Ryu

et al. 2016

ToxicolRes

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Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an IC50 value of 6.9, 16.8, and 43.1 μg/mL, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.

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“…The significant down-regulation of LCN2 mRNA was detected in ovarian cancer cells treated with estradiol and genistein, whereas the mRNA expression of ACE2 increased in the kidney after a high dose puerarin and apigenin treatment [ 21 , 22 , 23 ]. In addition, caffeic acid phenethyl ester and isoquercitrin induced a decrease in the CYP2B2 protein and mRNA level in the livers of Fischer 344 rats administered diethylnitrosamine [ 24 , 25 ]. Therefore, these results provide novel evidence that some genes listed in the present study may link the treatment of phytochemical compounds despite not showing a direct correlation between a single compound and each gene.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla

et al. 2015

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To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats.

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Cancer Prevention Mediated by Caffeic Acid Phenethyl Ester Involves Cyp2b1/2 Modulation in Hepatocarcinogenesis

Cited by 15 publications

References 27 publications

Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver

Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver

Inhibition of Cytochrome P450 by Propolis in Human Liver Microsomes

Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla

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