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

Hintzpeter, Jan; Hornung, Jan; Ebert, Bettina; Martin, H.; Maser, Edmund

doi:10.1016/j.cbi.2014.12.019

Cited by 24 publications

(13 citation statements)

References 63 publications

(74 reference statements)

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“…luteolin, apigenin, epigallocatechin gallate, curcumin) have shown a significant inhibitory effect on CBR1 in vitro (Arai et al, 2015, Carlquist et al, 2008Hintzpeter et al, 2015). Most of these studies have been aimed towards improving anthracycline therapy in cancer treatment (Forrest & Gonzalez, 2000;Olson et al, 1988Olson et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

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The modulation of carbonyl reductase 1 by polyphenols

Boušová

Skálová

Souček

et al. 2015

Drug Metabolism Reviews

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Carbonyl reductase 1 (CBR1), an enzyme belonging to the short-chain dehydrogenases/reductases family, has been detected in all human tissues. CBR1 catalyzes the reduction of many xenobiotics, including important drugs (e.g. anthracyclines, nabumetone, bupropion, dolasetron) and harmful carbonyls and quinones. Moreover, it participates in the metabolism of a number of endogenous compounds and it may play a role in certain pathologies. Plant polyphenols are not only present in many human food sources, but are also a component of many popular dietary supplements and herbal medicines. Many studies reviewed herein have demonstrated the potency of certain flavonoids, stilbenes and curcuminoids in the inhibition of the activity of CBR1. Interactions of these polyphenols with transcriptional factors, which regulate CBR1 expression, have also been reported in several studies. As CBR1 plays an important role in drug metabolism as well as in the protection of the organism against potentially harmful carbonyls, the modulation of its expression/activity may have significant pharmacological and/or toxicological consequences. Some polyphenols (e.g. luteolin, apigenin and curcumin) have been shown to be very potent CBR1 inhibitors. The inhibition of CBR1 seems useful regarding the increased efficacy of anthracycline therapy, but it may cause the worse detoxification of reactive carbonyls. Nevertheless, all known information about the interactions of polyphenols with CBR1 have only been based on the results of in vitro studies. With respect to the high importance of CBR1 and the frequent consumption of polyphenols, in vivo studies would be very helpful for the evaluation of risks/benefits of polyphenol interactions with CBR1.

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Section: Discussionmentioning

confidence: 99%

“…The experiments revealed curcumin as a tight-binding CBR1 inhibitor with a low IC 50 value of 382 nM and Ki value of 223 nM with respect to 2,3hexanedione (Hintzpeter et al, 2015). Curcumin also acts as an inhibitor for other reductases belonging to the AKR superfamily.…”

Section: The Inhibition Of Cbr1 By Polyphenolsmentioning

confidence: 96%

The modulation of carbonyl reductase 1 by polyphenols

Boušová

Skálová

Souček

et al. 2015

Drug Metabolism Reviews

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“…CUR can give up the potential to enhance the therapeutic effectiveness of daunorubicin by preventing heart tissue damage through the inhibition of CBR1 mediated reduction of daunorubicin to daunorubicinol. The inhibition of CBR1 can increase the efficacy of daunorubicin in cancer tissue and simultaneously decrease its cardiotoxicity 53 . Metabolic profile of Rhizoma paridis saponins combined with the turmeric intervention in H22 hepatocarcinoma mice tumor growth was validated by histopathological examination.…”

Section: Biological Activities Of Curcuminoidsmentioning

confidence: 99%

Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review

Amalraj¹,

Pius

Gopi

et al. 2017

Journal of Traditional and Complementary Medicine

699

413

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In recent years, several drugs have been developed deriving from traditional products and current drug research is actively investigating the possible therapeutic roles of many Ayruvedic and Traditional Indian medicinal therapies. Among those being investigated is Turmeric. Its most important active ingredient is curcuminoids. Curcuminoids are phenolic compounds commonly used as a spice, pigment and additive also utilized as a therapeutic agent used in several foods. Comprehensive research over the last century has revealed several important functions of curcuminoids. Various preclinical cell culture and animals studies suggest that curcuminoids have extensive biological activity as an antioxidant, neuroprotective, antitumor, anti-inflammatory, anti-acidogenic, radioprotective and arthritis. Different clinical trials also suggest a potential therapeutic role for curcuminoids in numerous chronic diseases such as colon cancer, lung cancer, breast cancer, inflammatory bowel diseases. The aim of this review is to summarize the chemistry, analog, metal complex, formulations of curcuminoids and their biological activities.

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“…Interestingly, the inhibitory potency of ebselen, and even more so that of ebselen diselenide, is comparable to that of curcumin, which is one of the more potent tight-binding inhibitors of human CBR1 (Hintzpeter et al, 2015). The inhibition pattern of ebselen as well as that of ebselen diselenide is noncompetitive (K i values of 5.586 6 0.254 and 3.782 6 0.189 mM, respectively), suggesting that the two compounds are capable of inhibiting NADPH-dependent reductases by binding equally well to the free enzyme or to the enzymesubstrate complex.…”

Section: Discussionmentioning

confidence: 97%

“…Because the evidence in this regard is still scarce and unsettled (Tanaka et al, 2005;Hintzpeter et al, 2015), we initially evaluated the effects on anthracycline reductive metabolism of a variety of compounds (metal chelators, radical scavengers, antioxidants, b-blockers, nitrone spin traps, and lipid-lowering drugs) employed as protective agents against anthracycline-induced cardiotoxicity. Among the compounds examined here, many failed to significantly inhibit anthracycline alcohol metabolite formation (see Table 1), thus confirming that their cardioprotective effects against anthracycline-induced cardiotoxicity should be ascribed to their antioxidant and/or antiapoptotic properties (Gianni et al, 2008;van Dalen et al, 2011;Octavia et al, 2012;Cardinale et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Anthracycline Alcohol Metabolite Formation in Human Heart Cytosol: A Potential Role for Several Promising Drugs

Mordente¹,

Silvestrini²,

Martorana³

et al. 2015

Drug Metab Dispos

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The clinical efficacy of anthracyclines (e.g., doxorubicin and daunorubicin) in cancer therapy is limited by their severe cardiotoxicity, the etiology of which is still not fully understood. The development of anthracycline-induced cardiomyopathy has been found to correlate with myocardial formation and accumulation of anthracycline secondary alcohol metabolites (e.g., doxorubicinol and daunorubicinol) that are produced by distinct cytosolic NADPH-dependent reductases. The aim of the current study is to identify chemical compounds capable of inhibiting myocardial reductases implied in anthracycline reductive metabolism in an attempt to decrease the production of cardiotoxic C-13 alcohol metabolites. Among the variety of tested compounds (metal chelators, radical scavengers, antioxidants, b-blockers, nitrone spin traps, and lipid-lowering drugs), ebselen, cyclopentenone prostaglandins, nitric oxide donors, and short-chain coenzyme Q analogs resulted in being effective inhibitors of both doxorubicinol and daunorubicinol formation. In particular, ebselen (as well as ebselen diselenide, its storage form in the cells) was the most potent inhibitor of cardiotoxic anthracycline alcohol metabolites with 50% inhibition of doxorubicinol formation at 0.2 mol Eq of ebselen with respect to doxorubicin concentration. The high efficacy, together with its favorable pharmacological profile (low toxicity, lack of adverse effects, and metabolic stability) portends ebselen as a promising cardioprotective agent against anthracycline-induced cardiotoxicity.

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

Cited by 24 publications

References 63 publications

The modulation of carbonyl reductase 1 by polyphenols

The modulation of carbonyl reductase 1 by polyphenols

Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review

Inhibition of Anthracycline Alcohol Metabolite Formation in Human Heart Cytosol: A Potential Role for Several Promising Drugs

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