• Proceedings of the PSK Conference
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• 2002.10a
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• pp.282.2-283
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• 2002

In situ and circulating estrogen is the most important endocrine hormone that promotes the growth of hormone-dependent breast cancer. Consequently. decrease of estrogen on in situ and circulation can inhibit breast cancer. Estrogen is mainly produced by the ovary in premenopausal women and by peripheral tissues such as adipose tissues in postmenopausal women. The cytochrome p450 (CYP19), aromatase. is a key enzyme in the synthesis of estrogen hormones. (omitted)

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.16-20
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• 2001

2-(Allylthio)pyrazine derivatives were designed as a novel cancer chemopreventive agent that functions through selective inhibtion of cytochrome P-450 and induction of phase 11 enzymes involved in the detoxification of carcinogens. A practical preparation method of 2-(allylthio) pyrazine derivatives was established by the reaction of 2-mercaptopyrazine and allylbromides in the presence of a catalytic antioxidant, DABCO (1,4-diazabicyclo[2,2,2] octane), in dimethyl-formamide at below $50^{\circ}C$.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.411.1-411.1
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• 2002

The purpose of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel orally coadministered in rats Paclitaxel is reported to be metabolized by cytochrome p-450(CYP3.A,)in both the liver and epithelial cells of small intestine and also absorption of paclitaxel is inhibited by p-glycoprotein efflux Pump in the intestinal mucosa. This resulted in poor orall bioavailability of paclitaxel. Area under the plasma concentration-time curve (AUC) of paclitaxel in combination with quercetin were significantly (p＜ 0.01) higher than those of control. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.301.1-301.1
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• 2002

The aim of present study was to investigate effects of blunt trauma on alterations in cytochrome P-450 (CYP)-dependent drug metabolizing function and to determine the role of Kupffer cells in the hepatocellular dysfunction Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia. Control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl3) was injected intravenously via the tail vein at 7.5 mg/kg body wt. 1 and 2 days before surgery. (omitted)

• BMB Reports
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• v.39 no.4
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• Biomedical Science Letters
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• v.25 no.1
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• pp.1-6
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• 2019

The hydroxylation of estradiol results in the formation of catechol estrogens such as 2-hydroxyestradiol ($2-OHE_2$) and 4-hydroxyestradiol ($4-OHE_2$). These catechol estrogens are further oxidized to quinone metabolites by peroxidases or cytochrome P450 (CYP450) enzymes. Catechol estrogens contribute to hormone-induced carcinogenesis by generating DNA adducts or reactive oxygen species (ROS). Interestingly, many of the natural products found in living organisms have been reported to show protective effects against carcinogenesis induced by catechol estrogens. Although some compounds have been reported to increase the activity of catechol estrogens via oxidation to quinone metabolites, many natural products decreased the activity of catechol estrogens by inhibiting DNA adduct formation, ROS production, or oxidative cell damage. Here we focus specifically on the chemopreventive effects of these natural compounds against carcinogenesis induced by catechol estrogens.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6101-6104
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• 2012

Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative $C_t$ (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.8.1-8.14
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• 2018

We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Our screening of the CYP2J family indicated a dysregulation in the CYP system in a cerebellar-specific manner. Moreover, in Purkinje cells, CYP2J6 showed an elevated expression level compared to that of astrocytes, granule cells, and microglia. In this regard, we found that one CYP metabolite, 14,15-EET, acts as a key mediator in ameliorating cholesterol accumulation. In confirming this hypothesis, 14,15-EET treatment reduced the accumulation of cholesterol in human NPC1 patient-derived fibroblasts in vitro by suppressing cholesterol synthesis and ameliorating the impaired autophagic flux. We show that the reduced activity within the CYP system in the cerebellum could cause the neurological symptoms of NPC1 patients, as 14,15-EET treatment significantly rescued cholesterol accumulation and impaired autophagy. We also provide evidence that the intranasal administration of hUCB-MSCs is a highly promising alternative to traumatic surgical transplantation for NPC1 patients.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.129-136
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• 2013

Objectives: Among many new drugs that are under investigation with intent to treat cancer, oral kinase inhibitors are proven to be effective in numerous clinical trials and easy to administer. Due to these advantages the use of oral kinase inhibitors is increasing. Oral kinase inhibitors are metabolized by CYP450 which can result either increase of adverse effect or decrease of drug effect by drug interaction when used concurrently with other agents. In this research, the medication records of patients on oral kinase inhibitors from Oct. 2010 to Nov. 2011 were reviewed to investigate potential drug interactions. Methods: From Oct. 2010 to Nov. 2011, cancer patients in Inha University Hospital who took oral kinase inhibitors more than once were included. The patients' medication records were reviewed to list out concurrent medications that have interaction potential with oral kinase inhibitors, the frequency of concurrent use, and the severity of interaction result using Micromedex$^{(R)}$ and Lexicomp-online$^{(R)}$ as references. Results: As a result, 90 cases of drug with interaction potential were prescribed by Micromedex$^{(R)}$ and 179 cases by Lexicomp-online$^{(R)}$ data. In case of severity, 33.3% by Micromedex$^{(R)}$ and 26.3% by Lexicomp-online$^{(R)}$ were categorized as Major and 65.6% by Micromedex$^{(R)}$ and 72.6% by Lexicomp-online$^{(R)}$ as Moderate. The number of adverse events was 92 cases which 58.7% were on skin and 19.6% on Gastro-intestinal tract. Conclusions: Considerable number of drug with interaction potential was used though each oral kinase inhibitors showed differences in extent. Hence there exists the risk of drug interaction in patients taking oral kinase inhibitors with other drugs.

• Toxicological Research
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• v.14 no.3
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• pp.321-328
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• 1998

This study was performed to evaluate the effect of liver damage on toluene metabolism in rats pretreated with carbon tetachloride. Liver damage in rats was induced by administration of 0.1ml of carbon tetrachloride per 100g of body wight intraperitoneally every day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to the animals instead of carbon tetrachloride. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of carbon tetachloride. Based on the histopathological findings, liver weight and serum alanine aminotransferase, the $CCl_4$-preteated group was found to have gradual severe liver damage. Especially the degree of liver injury became increasingly severe throughout the whole course of the experiment. The contnts of hippuric acid in urine lower in the all groups pretreated with $CCl_4$than that of the control. The contents of hepatic cytochrome P450(CYP), benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were decreased in $CCl_4$-pretreated rats than those of the control. The $CCl_4$treated animals showed the gradual decreased activities of these enzyme as injection times elapsed. Km values of the benzylalcohol dehydrogenase in pooled liver samples from $CCl_4$-pretreated or control groups were similar. On the other hand, Vmax values of the $CCl_4$-pretreated group was lower than of the control. Therefore, it can be concluded that reduction of the toluene metabolism in damaged rat liver induced with $CCl_4$was due to the inhibition of CYP content, bezylalcohol and benzaldehyde dehydrogenase activities which related with toluene metabolic enzyme system.