A hydroxylated flavonol, fisetin inhibits the formation of a carcinogenic estrogen metabolite

Meng, Xiangyu; Sun, Hui; Yang, Lianrong; Yin, Rui; Qi, Lehui

doi:10.1016/j.steroids.2017.01.002

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…In the management of breast cancer, aim is to preserve quality of life with prolonged life expectancy. The use of bioflavonoids may inhibit estrogen formation [ 150 ]. Effective communication between doctors and patients plays an important role to improve clinical outcome.…”

Section: Diagnosismentioning

confidence: 99%

Awareness and current knowledge of breast cancer

Akram¹,

et al. 2017

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Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

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Section: Diagnosismentioning

confidence: 99%

Awareness and current knowledge of breast cancer

Akram¹,

et al. 2017

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“…Additionally, this concentration was in the vicinity of the K m value of 7.14 μM (described later in Table ) for the 4‐hydroxylation. Furthermore, a previous study showed that this concentration was appropriate for evaluating the inhibition and kinetics of human recombinant CYP1‐mediated 17β‐estradiol hydroxylation in vitro (Meng et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…The glycoside of oroxylin A also had a significant inhibitory potency towards CYP1B1 (Tables and ). Moreover, the inhibitory effect of oroxylin A for CYP1B1 with IC 50 value of 0.0146 μM and K i value of 0.00547 μM was even stronger than that of fisetin and flavone, which had been suggested as extreme potent inhibitors of 4‐hydroxylation of 17β‐estradiol in vitro (Meng et al, ). Further enzyme inhibition kinetic analysis suggested that baicalein, oroxylin A, and the glycoside of oroxylin A inhibited human recombinant CYP1B1 with a mixed mechanism (Tables and and Figure ).…”

Section: Discussionmentioning

confidence: 97%

“…Incubation with 17β‐estradiol as substrate was performed as previously reported with slight modifications (Meng, Sun, Yang, Yin, & Qi, ; Takemura et al, ). Briefly, incubation mixtures contained 0.05 mg/ml of human recombinant CYP1A1 or 1B1 (Cypex, Dundee, UK), 5‐mM MgCl 2 , 1‐mM NADPH, 20‐μM 17β‐estradiol (Meng et al, ; Takemura, Uchiyama, et al, ), and varying concentrations of baicalein, baicalin, oroxylin A, or oroxylin A 7‐O‐β‐D‐glucuronide in 0.2 ml of phosphate buffered saline (0.15 M, pH 7.4). Stock solutions of flavonoids were prepared in dimethyl sulfoxide.…”

Section: Methodsmentioning

confidence: 99%

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Oroxylin A, a methylated metabolite of baicalein, exhibits a stronger inhibitory effect than baicalein on the CYP1B1‐mediated carcinogenic estradiol metabolite formation

Song

et al. 2019

Phytotherapy Research

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4-OHE2) from 17β-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17β-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway. In this study, inhibitory effects of flavonoids baicalein and oroxylin A, a metabolite of baicalein in human body, on CYP1A1 and 1B1 activities were investigated in vitro. The inhibition intensities of baicalein and oroxylin A towards CYP1B1 were greater than towards CYP1A1 with a mixed mechanism. In addition, oroxylin A showed a stronger inhibitory effect than baicalein towards the CYP1B1-mediated 17β-estradiol 4-hydroxylation, with the IC 50 values of 0.0146 and 2.27 μM, respectively. Docking studies elucidated that oroxylin A had a stronger binding affinity than baicalein for CYP1B1. In MCF-7 cells, compared with baicalein-treated groups, oroxylin A with lower doses decreased and increased the formation of 4-OHE2 and 2-hydroxyestradiol, respectively, with a preferential induction of mRNA of CYP1A1 over CYP1B1. In conclusion, this study demonstrated that oroxylin A showed a stronger inhibitory effect than baicalein on CYP1B1-mediated 4-OHE2 formation in MCF-7 cells, providing crucial implications for their possibly preventive/therapeutic potential against breast cancer via inhibition of CYP1B1, particularly of oroxylin A.

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“…Therefore, in this investigation, two steroid derivatives were prepared to characterize their interaction with 17β-HD type 1; the first stage was achieved by the synthesis of two steroid derivatives as follows: Preparation of a steroid-imino-derivative (2.) There are several reports to synthesis of imino-derivatives using some reagents such as iron or cobalt [22], ClCH 2 COCl/Et 3 N [23], Iodide [24], KSCN/Br 2 [25], HOAc [26] and others. In this study, the estradiol-ethylenediamine reacted with 2-hydroxy-1naphthaldehyde to form a hydroxynaphthalen-steroid derivative (2).…”

Section: Resultsmentioning

confidence: 99%

Preparation of two steroid derivatives and its theoretical interaction with a 17β‐hydroxysteroid dehydrogenase type 1

2019

Biointerface Res Appl Chem

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The aim of this study was synthesizing two steroid derivatives to evaluate their theoretical interact with a 17β‐hydroxysteroid dehydrogenase type 1. The first stage was achieved by the preparation of a steroid-imino analog (compound 2) using a reaction of imination and ii) etherification. Then, the theoretical interact of two steroid analogs with 17β‐hydroxysteroid dehydrogenase type 1 (1IOL) was evaluated using fisetin and methyl paraben as controls in a docking model. The results suggest that steroid derivatives could interact via a different type of aminoacid residues of 1IOL protein surface. However, the compound 2 showed a constant of inhibition lower compared with fisetin, methyl paraben and compound 3. All these data indicate that steroid derivative could act as 17β‐hydroxysteroid dehydrogenase type 1 inhibitor.

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A hydroxylated flavonol, fisetin inhibits the formation of a carcinogenic estrogen metabolite

Cited by 12 publications

References 23 publications

Awareness and current knowledge of breast cancer

Awareness and current knowledge of breast cancer

Oroxylin A, a methylated metabolite of baicalein, exhibits a stronger inhibitory effect than baicalein on the CYP1B1‐mediated carcinogenic estradiol metabolite formation

Preparation of two steroid derivatives and its theoretical interaction with a 17β‐hydroxysteroid dehydrogenase type 1

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