Differential Effects of <i>Glycyrrhiza</i> Species on Genotoxic Estrogen Metabolism: Licochalcone A Downregulates P450 1B1, whereas Isoliquiritigenin Stimulates It

Dunlap, Tareisha; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

doi:10.1021/acs.chemrestox.5b00157

Cited by 28 publications

(86 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,32,49−51 However, the AhR mediated P450 1A1/1B1 induction in MCF-10A cells is relatively low as reported previously 36 and confirmed in the present study. Data also suggest that the Phase I and Phase II enzyme expression is variable in MCF-10A cells depending on the confluence level in cell culture.…”

Section: Discussionsupporting

confidence: 91%

“…MCF-10A cells were cultured in 1:1 Dulbecco’s modified Eagle medium and Ham’s F12 nutrient mixture (DMEM/F12) with 15 mM HEPES and l -glutamine (Invitrogen), supplemented with 20 ng/mL epidermal growth factor, 100 ng/mL cholera toxin, 0.5 μg/mL hydrocortisone, 10 μg/mL insulin, 5% horse serum, and 1% penicillin–streptomycin at 37 °C with 5% CO 2 as described previously. 32 MCF-7 cells were maintained in RPMI 1640 media supplemented with 10% fetal bovine serum, 1% glutamax, 1% AB/AM, 1% nonessential amino acids, and 3 μg/mL insulin. All experiments were done with cells under 15 passages in phenol-red free media supplemented with charcoal stripped serum and the same other ingredients.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…32 The total RNA was extracted according to Qiagen’s (Valencia, CA) RNeasy kit instructions. RNA was reverse transcribed according to Invitrogen’s SuperScript III First-Strand Synthesis System for RT-PCR.…”

Section: Materials and Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Hop (Humulus lupulus L.) Extract and 6-Prenylnaringenin Induce P450 1A1 Catalyzed Estrogen 2-Hydroxylation

Wang

Dunlap

Howell

et al. 2016

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

Humulus lupulus L. (hops) is a popular botanical dietary supplement used by women as a sleep aid and for postmenopausal symptom relief. In addition to its efficacy for menopausal symptoms, hops can also modulate the chemical estrogen carcinogenesis pathway and potentially protect women from breast cancer. In the present study, an enriched hop extract and the key bioactive compounds [6-prenylnarigenin (6-PN), 8-prenylnarigenin (8-PN), isoxanthohumol (IX), and xanthohumol (XH)] were tested for their effects on estrogen metabolism in breast cells (MCF-10A and MCF-7). The methoxyestrones (2-/4-MeOE1) were analyzed as biomarkers for the nontoxic P450 1A1 catalyzed 2-hydroxylation and the genotoxic P450 1B1 catalyzed 4-hydroxylation pathways, respectively. The results indicated that the hop extract and 6-PN preferentially induced the 2-hydroxylation pathway in both cell lines. 8-PN only showed slight up-regulation of metabolism in MCF-7 cells, whereas IX and XH did not have significant effects in either cell line. To further explore the influence of hops and its bioactive marker compounds on P450 1A1/1B1, mRNA expression and ethoxyresorufin O-dealkylase (EROD) activity were measured. The results correlated with the metabolism data and showed that hop extract and 6-PN preferentially enhanced P450 1A1 mRNA expression and increased P450 1A1/1B1 activity. The aryl hydrocarbon receptor (AhR) activation by the isolated compounds was tested using xenobiotic response element (XRE) luciferase construct transfected cells. 6-PN was found to be an AhR agonist that significantly induced XRE activation and inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced XRE activity. 6-PN mediated induction of EROD activity was also inhibited by the AhR antagonist CH223191. These data show that the hop extract and 6-PN preferentially enhance the nontoxic estrogen 2-hydroxylation pathway through AhR mediated up-regulation of P450 1A1, which further emphasizes the importance of standardization of botanical extracts to multiple chemical markers for both safety and desired bioactivity.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Materials and Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Hop (Humulus lupulus L.) Extract and 6-Prenylnaringenin Induce P450 1A1 Catalyzed Estrogen 2-Hydroxylation

Wang

Dunlap

Howell

et al. 2016

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…19,23 However, studies comparing the biological properties of authenticated Glycyrrhiza species are rare. 49,50 At the same time, this kind of study design is paramount for the adequate chemical and biological standardization.…”

Section: Resultsmentioning

confidence: 99%

Metabolite Profiling and Classification of DNA-Authenticated Licorice Botanicals

et al. 2015

Self Cite

View full text Add to dashboard Cite

Raw licorice roots represent heterogeneous materials obtained from mainly three Glycyrrhiza species. G. glabra, G. uralensis, and G. inflata exhibit marked metabolite differences in terms of flavanones (Fs), chalcones (Cs), and other phenolic constituents. The principal objective of this work was to develop complementary chemometric models for the metabolite profiling, classification, and quality control of authenticated licorice. A total of 51 commercial and macroscopically verified samples were DNA authenticated. Principal component analysis and canonical discriminant analysis were performed on 1H NMR spectra and area under the curve values obtained from UHPLC-UV chromatograms, respectively. The developed chemometric models enable the identification and classification of Glycyrrhiza species according to their composition in major Fs, Cs, and species specific phenolic compounds. Further key outcomes demonstrated that DNA authentication combined with chemometric analyses enabled the characterization of mixtures, hybrids, and species outliers. This study provides a new foundation for the botanical and chemical authentication, classification, and metabolomic characterization of crude licorice botanicals and derived materials. Collectively, the proposed methods offer a comprehensive approach for the quality control of licorice as one of the most widely used botanical dietary supplements.

show abstract

“…Licochalcone A, an anti-inflammatory [1][2][3][4], immunomodulatory [5,6], and antimicrobial [3,5,[7][8][9] polyphenol extracted from Glycyrrhiza inflata [1][2][3]10], triggers apoptosis or inhibits proliferation and migration of tumor cells [11], including those of cervical cancer [12], oral squamous carcinoma [7,9,[13][14][15], esophageal carcinoma [16], gastric cancer [4,17,18], hepatocellular carcinoma [2,19], malignant pleural mesothelioma [20], bladder determined photometrically at 405 nm. The absorption of the supernatant of erythrocytes lysed in distilled water was defined as 100% hemolysis.…”

Section: Introductionmentioning

confidence: 99%

Licochalcone A Induced Suicidal Death of Human Erythrocytes

Egler

Läng

2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: The anti-inflammatory, immunomodulatory, and antimicrobial Glycyrrhiza inflata extract component licochalcone A triggers apoptosis of tumor cells and is thus considered for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the triggering of eryptosis includes Ca²⁺ entry with increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), and ceramide. The present study explored, whether and how licochalcone A induces eryptosis. Methods: Human erythrocytes drawn from healthy individuals were exposed for 24 hours to 1-10 µg/ml licochalcone A. Flow cytometry was subsequently employed to estimate phosphatidylserine exposure at the cell surface from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, and ceramide utilizing specific antibodies. In addition, hemolysis was quantified from hemoglobin release. Results: Licochalcone A significantly increased the percentage of annexin-V-binding cells (≥ 5 µg/ml), significantly decreased forward scatter (2.5 - 5 µg/ml), significantly increased Fluo3-fluorescence (≥ 7.5 µg/ml), and significantly increased ceramide abundance (10 µg/ml). The effect of licochalcone on annexin-V-binding was not significantly modified, but hemolysis significantly enhanced by removal of extracellular Ca²⁺. Conclusions: Licochalcone triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect independent from Ca²⁺ entry and presumably in part due to ceramide.

show abstract

Differential Effects of Glycyrrhiza Species on Genotoxic Estrogen Metabolism: Licochalcone A Downregulates P450 1B1, whereas Isoliquiritigenin Stimulates It

Cited by 28 publications

References 70 publications

Hop (Humulus lupulus L.) Extract and 6-Prenylnaringenin Induce P450 1A1 Catalyzed Estrogen 2-Hydroxylation

Hop (Humulus lupulus L.) Extract and 6-Prenylnaringenin Induce P450 1A1 Catalyzed Estrogen 2-Hydroxylation

Metabolite Profiling and Classification of DNA-Authenticated Licorice Botanicals

Licochalcone A Induced Suicidal Death of Human Erythrocytes

Contact Info

Product

Resources

About