Anthracyclines and their metabolism in human liver microsomes and the participation of the new microsomal carbonyl reductase

Skarka, Adam; Škarydová, Lucie; Štambergová, Hana; Wsól, Vladimı́r

doi:10.1016/j.cbi.2010.12.016

Cited by 32 publications

(17 citation statements)

References 35 publications

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“…DOX was detected on an Agilent 1290 Series UHPLC chromatographic system (Agilent, Santa Clara, CA, USA) equipped with a Zorbax C18 Eclipse Plus (2.1 × 50 mm, 1.8 μm) column with a 1290 Infinity inline filter (Agilent). The HPLC method used by Skarka [ 28 ] was adapted to a UHPLC system: isocratic elution of 1.0 mL/min by 0.1% formic acid in water and acetonitrile in ratio 76:24; 30 °C thermostatic column compartment; fluorescence detection at λex = 480 nm and λem = 560 nm. Chemical standards were purchased from Toronto Research Chemicals (Toronto, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant Cancer Cell Lines

et al. 2017

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β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER) and valencene (VAL) are constituents of the essential oil of Myrica rubra (MEO), which has significant antiproliferative effect in various cancer cell lines. In the present study, we compared the antiproliferative effect of these sesquiterpenes alone and in combination with the cytostatic drug doxorubicin (DOX) in cancer cell lines with different sensitivity to DOX. Two ovarian cancer cell lines (sensitive A2780 and partly resistant SKOV3) and two lymphoblast cancer cell lines (sensitive CCRF/CEM and completely resistant CEM/ADR) were used. The observed effects varied among sesquiterpenes and also differed in individual cell lines, with only VAL being effective in all the cell lines. A strong synergism of DOX with NER was found in the A2780 cells, while DOX acted synergistically with HUM and CAO in the SKOV3 cells. In the CCRF/CEM cells, a synergism of DOX with CAO and NER was observed. In resistant CEM/ADR cells, sesquiterpenes did not increase DOX efficacy, although they significantly increased accumulation of DOX (up to 10-times) and rhodamine-123 (substrate of efflux transporter ABCB1) within cancer cells. In conclusion, the tested sesquiterpenes were able to improve DOX efficacy in the sensitive and partly resistant cancer cells, but not in cells completely resistant to DOX.

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Section: Methodsmentioning

confidence: 99%

The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant Cancer Cell Lines

et al. 2017

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“…Deregulation of Aldo-Keto Reductases in HCC. Aldoketo reductases (AKRs) are involved in the phase I metabolism of numerous endogenous and xenobiotic compounds including steroids, carbohydrates, prostaglandins, aldehydes, ketones, and many therapeutic drugs such as the cytotoxic anthracyclines (e.g., doxorubicin, daunorubicin, and idarubicin) (Novotna et al, 2008;Skarka et al, 2011;Matsunaga et al, 2012;Penning, 2015). There are 15 AKR genes in the human genome (Penning, 2015) but none of these genes are classified as ADME genes by the Phar-maADME consortium (pharmadame.org).…”

Section: % Of the Patients (Supplementalmentioning

confidence: 99%

Deregulation of the Genes that Are Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Hepatocellular Carcinoma

Marri

Mackenzie

et al. 2018

J Pharmacol Exp Ther

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Genes involved in drug absorption, distribution, metabolism, and excretion (ADME) are called ADME genes. Currently, 298 genes that encode phase I and II drug metabolizing enzymes, transporters, and modifiers are designated as ADME genes by the PharmaADME Consortium. ADME genes are highly expressed in the liver and their levels can be influenced by liver diseases such as hepatocellular carcinoma (HCC). In this study, we obtained RNA-sequencing and microRNA (miRNA)-sequencing data from 371 HCC patients via The Cancer Genome Atlas liver hepatocellular carcinoma project and performed ADME gene-targeted differential gene expression analysis and expression correlation analysis. Two hundred thirty-three of the 298 ADME genes (78%) were expressed in HCC. Of these genes, almost one-quarter (58 genes) were significantly downregulated, while only 6% (15) were upregulated in HCC relative to healthy liver. Moreover, one-half (14/28

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“…Instead of the cytosolic fraction crude A549 cell lysates have been used to ensure the involvement of all DAUN reductases in this cancer cell line. This also includes the recently discovered microsomal reductase, which seems to be participating in anthracycline metabolism [37]. The presence of other reductases not inhibited by curcumin may explain the fact that despite the low K i -value for CBR1, residual activity was 40% even in the presence of 50 lM curcumin.…”

Section: Discussionmentioning

confidence: 98%

Curcumin is a tight-binding inhibitor of the most efficient human daunorubicin reductase – Carbonyl reductase 1

Hintzpeter¹,

Hornung²,

Ebert³

et al. 2015

Chemico-Biological Interactions

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Anthracyclines and their metabolism in human liver microsomes and the participation of the new microsomal carbonyl reductase

Cited by 32 publications

References 35 publications

The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant Cancer Cell Lines

The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant Cancer Cell Lines

Deregulation of the Genes that Are Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Hepatocellular Carcinoma

Curcumin is a tight-binding inhibitor of the most efficient human daunorubicin reductase – Carbonyl reductase 1

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