木脂素分解产物enterolactone和enterodiol对成骨细胞样细胞MG63的双相作用

目的:观察enterolactone和enterodiol对成骨细胞样细胞MG63的作用。方法:用MTT法检测观察enterolactone和enterodiol对MG63细胞生长的影响,用碱性磷酸酶活性检测观察enterolactone和enterodiol对MG63细胞活性的影响,用逆转录聚合酶链反应(RT-PCR)观察enterolactone和enterodiol对MG63细胞碱性磷酸酶、骨钙素、Ⅰ型胶原基因表达水平的影响。结果:Enterolactone和enterodiol在0.01 mg/mL浓度时能增加MG63细胞的活力。随着浓度的增加,细胞活力逐渐减弱。Enterolactone和en-terodiol对MG63细胞碱性磷酸酶活性的影响与对MG63细胞生长的影响基本一致,也是在低浓度时增加其活性,在高浓度时抑制其活性。En-terolactone和enterodiol都能增加MG63细胞碱性磷酸酶、骨钙素和Ⅰ型胶原的基因转录。结论:Enterolactone和enterodiol在低浓度时能增进成骨细胞的活性,在高浓度时抑制其活性,对成骨细胞有双相调节作用。

Enterolactone modulates the ERK/NF-κB/Snail signaling pathway in triple-negative breast cancer cell line MDA-MB-231 to revert the TGF-β-induced epithelial–mesenchymal transition

Objective:Triple-negative breast cancer(TNBC)is highly metastatic,and there is an urgent unmet need to develop novel therapeutic strategies leading to the new drug discoveries against metastasis.The transforming growth factor-β(TGF-β)is known to promote the invasive and migratory potential of breast cancer cells through induction of epithelial–mesenchymal transition(EMT)via the ERK/NF-κB/Snail signaling pathway,leading to breast cancer metastasis.Targeting this pathway to revert the EMT would be an attractive,novel therapeutic strategy to halt breast cancer metastasis.Methods:Effects of enterolactone(EL)on the cell cycle and apoptosis were investigated using flow cytometry and a cleaved caspase-3 enzyme-linked immunosorbent assay(ELISA),respectively.Effects of TGF-βinduction and EL treatment on the functional malignancy of MDA-MB-231 breast cancer cells were investigated using migration and chemo-invasion assays.The effects of EL on EMT markers and the ERK/NF-κB/Snail signaling pathway after TGF-βinduction were studied using confocal microscopy,quantitative reverse transcription polymerase chain reaction(q RT-PCR),Western blot,and flow cytometry.Results:Herein,we report that EL exhibits a significant antimetastatic effect on MDA-MB-231 cells by almost reverting the TGF-β-induced EMT in vitro.EL downregulates the mesenchymal markers N-cadherin and vimentin,and upregulates the epithelial markers E-cadherin and occludin.It represses actin stress fiber formation via inhibition of mitogen-activated protein kinase p-38(MAPK-p38)and cluster of differentiation 44(CD44).EL also suppresses ERK-1/2,NF-κB,and Snail at the m RNA and protein levels.Conclusions:Briefly,EL was found to inhibit TGF-β-induced EMT by blocking the ERK/NF-κB/Snail signaling pathway,which is a promising target for breast cancer metastasis therapy.

Antioxidant Activity of Substituted Enterolactone Derivatives in the Gas Phase and Water

The antioxidant activity of ortho and meta substituted Enterolactone derivatives has been investigated in the gas phase and water.The reaction enthalpies of antioxidant activity of the studied derivatives have been calculated and compared with the corresponding values of Enterolactone.Results show that EWG substituents increase the BDE and IP,while the EDG ones rise in the PA.The Enterolactone derivatives with the lowest BDE,IP and PA values were identified as the compounds with high antioxidant activity.Results show that the substituents in the ortho position have high potential for the synthesis of novel Enterolactone derivatives.Results show that Enterolactone derivatives can processes their protective role via HAT and SPLET mechanism in gas phase and solvent,respectively.The calculated reaction enthalpies of the substituted Enterolactones have linear dependence with Hammett constants and EHOMO that can be utilized in the selection of suitable substituents for the synthesis of novel antioxidants based on Enterolactone.