Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells

Chen, Yan; Wang, Jing; Hong, Duan‑Yang; Chen, Lin; Zhang, Yanyan; Xu, Yini; Pan, Di; Fu, Lingyun; Tao, Ling; Luo, Hong; Shen, Xiangchun

doi:10.18632/oncotarget.14433

Cited by 22 publications

(20 citation statements)

References 51 publications

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“…The crystal structure of β-catenin (PDB entry: 2Z6H) was used to generate the SP141-β-catenin binding complex. The SYBYL/Sketch module was applied to construct the structure of SP141, which was further optimized using Powell’s method and then assigned to SYBYL-X 2.0 software using the Gasteiger–Hückel method ( Joshi et al, 2016 ; Chen et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy

Qin

Wang

et al. 2018

Front. Pharmacol.

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The β-catenin and MDM2 oncoproteins are overexpressed and constitutively activated in human pancreatic cancer and contribute to its initiation, progression, and metastasis. The Wnt/β-catenin signaling pathway strongly interacts with the MDM2-p53 signaling pathway, accelerating the tumorigenesis and its development. Therefore, therapies inhibiting both β-catenin and MDM2 are suggested to be ideal treatments for patients with advanced pancreatic cancer. We have recently identified a novel class of β-carboline compounds as the specific and potent MDM2 inhibitors, including a lead compound SP141. In the present study, we utilized SP141 as an exemplary β-carboline compound to characterize β-catenin as a molecular target of the β-carboline compounds and to demonstrate an important role of β-catenin in the anticancer activity of β-carboline. We found that the silencing of either β-catenin or MDM2 largely reduced the anticancer activity of SP141 while the double silencing of both genes almost completely blocked SP141’s activity. SP141 directly bound to β-catenin and inhibited its expression and activity in pancreatic cancer cells in vitro and in vivo. The inhibitory effects of SP141 on β-catenin were mediated by the ubiquitin–proteasome system in an MDM2-independent manner. In conclusion, these results suggest that SP141 exerts its anticancer activity by dually inhibiting β-catenin and MDM2. We envision that β-carboline derivatives can be developed as promising dual inhibitors of β-catenin and MDM2 for the treatment of advanced pancreatic cancer.

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Section: Methodsmentioning

confidence: 99%

Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy

Qin

Wang

et al. 2018

Front. Pharmacol.

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“…Through these two pathways, estrogen can participate in cell growth, differentiation, and apoptosis. 8,[24][25][26][27] Besides, it also plays an important role in immune regulation. 28 To gain a better understanding of how E2 inhibited the expres- estrogen receptor pathway and membrane estrogen receptor pathway might be involved in the mechanism.…”

Section: Discussionmentioning

confidence: 99%

Regulatory effect of 17β‐estradiol on the expression of β‐defensin‐2 and proinflammatory cytokines in human oral epithelial cells

Tang

Chen

et al. 2020

J Oral Pathology Medicine

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Background:Although estrogen deficiency has been proposed as a risk factor for oral mucosal inflammatory diseases in post-menopausal women, the mechanisms involved remain unclear. This study aimed to investigate the effect of 17β-estradiol (E2) on the inflammatory response stimulated by interleukin-1 beta (IL-1β) in human oral mucosal epithelial cells (hOMECs) and its possible mechanism.Methods: Primary hOMECs were obtained from female infants and cultured in keratinocyte growth medium. The hOMECs at second passage were collected and stimulated by 10 −7 mol/L ICI182,780 or 10 −7 mol/L G1 for 1 hour, E2 (10 −7 mol/L, 10 −8 mol/L, 10 −9 mol/L) for 36 hour, 100 ng/mL IL-1β for 12 hours, respectively.Human beta-2 defensin (hBD-2), tumor necrosis factor-alpha (TNF)-α, IL-6, IL-8, estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30) mRNA levels and protein levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western Blot (WB), respectively.Results: Expression of hBD-2 and inflammatory cytokines increased after IL-1β stimulation, which was down-regulated by E2 pre-treatment. With ICI182,780, the suppression of E2 on hBD-2 mRNA was attenuated. With G1, the mRNA expression and protein expression of hBD-2 were reduced. Conclusion:Pre-treatment of hOMECs with E2 at physiological concentrations inhibited the IL-1β-induced expression of hBD-2 and inflammatory cytokines. The protective effects of E2 suggest its potential use treating oral inflammatory diseases in clinical practice. K E Y W O R D S17β-estradiol, estrogen receptors, human oral mucosal epithelial cells, inflammatory cytokines, regulatory effect

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“…These seven flavonoids were all reported to bind estrogen receptors and/or interact with estrogen receptor signaling [ 40 , 41 ]. A docking simulation between bacalein and human estrogen receptor was also reported [ 42 ]. Estrogen has been reported to modulate the differentiation, maturation, lifespan, and effector functions of innate immune cells, including neutrophils, macrophages, natural killer cells, and dendritic cells [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Study of Bioactive Flavonoids in the Traditional Japanese Medicine Keigairengyoto Exerting Antibacterial Effects against Staphylococcus aureus

Mutoh

Kaneko

Koseki

et al. 2018

IJMS

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Recent studies have demonstrated that flavonoid glucuronides can be deconjugated to the active form aglycone by β-glucuronidase-expressing macrophages. Keigairengyoto (KRT) is a flavonoid-rich traditional Japanese medicine reported to enhance bacterial clearance through immune modulation. Our aims are to examine the pharmacokinetics of KRT flavonoids and to identify active flavonoids contributing to the adjuvant effects of KRT. KRT was evaluated at pharmacokinetic analysis to quantify absorbed flavonoids, and cutaneous infection assay induced in mice by inoculation of Staphylococcus aureus. Preventive or therapeutic KRT administration reduced the number of bacteria in the infection site as well as macroscopic and microscopic lesion scores with efficacies similar to antibiotics. Pharmacokinetic study revealed low plasma levels of flavonoid aglycones after KRT administration; however, plasma concentrations were enhanced markedly by β-glucuronidase treatment, with baicalein the most abundant (Cmax, 1.32 µg/mL). In random screening assays, flavonoids such as bacalein, genistein, and apigenin enhanced bacteria phagocytosis by macrophages. Glucuronide bacalin was converted to aglycone baicalein by incubation with living macrophages, macrophage lysate, or skin homogenate. Taken together, the adjuvant effect of KRT may be due to some blood-absorbed flavonoids which enhance macrophage functions in host defense. Flavonoid-rich KRT may be a beneficial treatment for infectious skin inflammation.

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Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells

Cited by 22 publications

References 51 publications

Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy

Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy

Regulatory effect of 17β‐estradiol on the expression of β‐defensin‐2 and proinflammatory cytokines in human oral epithelial cells

Pharmacokinetic Study of Bioactive Flavonoids in the Traditional Japanese Medicine Keigairengyoto Exerting Antibacterial Effects against Staphylococcus aureus

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