Oxymatrine Promotes S-Phase Arrest and Inhibits Cell Proliferation of Human Breast Cancer Cells &lt;i&gt;in Vitro&lt;/i&gt; through Mitochondria-Mediated Apoptosis

Wu, Jie; Cai, Yan; Li, Maolan; Zhang, Yijian; Li, Huai-Feng; Tan, Zhen

doi:10.1248/bpb.b17-00010

Cited by 26 publications

(15 citation statements)

References 24 publications

(23 reference statements)

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“…The B-cell/leukemia-2 (Bcl-2), cleaved PARP and caspase-3 proteins were reported as the key proteins in regulating cell apoptosis. Decreased Bcl-2 or increased cleaved PARP and caspase-3 will promote cell apoptosis (27). In the present study, we found that lenalidomide and cisplatin induces caspases-3 activity and cleaved PARP expression, while reduces Bcl-2 expression.…”

Section: Discussionsupporting

confidence: 59%

Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells inï¿½vitro

et al. 2018

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Abstract.Lenalidomide is an immunomodulatory drug and possesses anti-angiogenic and immunomodulatory activities against multiple myeloma. The present study assessed the in vitro effect of lenalidomide combined with cisplatin on MDA-MB-231, a triple-negative breast cancer (TNBC) cell line and explored the underlying molecular mechanism of this combination. Cell viability, apoptosis and the protein expression of phosphorylated (p) and total extracellular signal-regulated kinase (ERK), B-cell lymphoma-2 (Bcl-2), caspase-3, cleaved poly-adenosine diphosphate-ribose polymerase (cPARP), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured in MDA-MB-231 cells treated with different concentrations of lenalidomide, cisplatin and their combination using different biochemical assays. Lenalidomide demonstrated no significant effect on the cell viability of MDA-MB-231 cells, even at high concentrations, whereas lenalidomide in combination with cisplatin, significantly reduced cisplatin IC 50 from 7.8 to 3.0 µM in MDA-MB-231 cells. In addition, lenalidomide and cisplatin in combination significantly induced cell apoptosis by 1.6-and 1.38-fold, respectively compared with lenalidomide and cisplatin alone (P<0.05). The expression levels of VEGF, bFGF and Bcl-2 proteins were significantly reduced (P<0.01), whereas caspase-3 and cleaved PARP expression were significantly increased in MDA-MB-231 cells treated with the combination compared to those treated with single agents (P<0.01). Lenalidomide treatment alone significantly reduced the p-ERK level compared with the control (P<0.05) and cisplatin treatment alone significantly increased it (P<0.01), however treatment with them in combination significantly reduced the p-ERK level in MDA-MB-231 cells compared with cisplatin treatment alone (P<0.05). In conclusion, the present study provides the basis for using lenalidomide in combination with cisplatin in TNBC therapy.

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Section: Discussionsupporting

confidence: 59%

Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells inï¿½vitro

et al. 2018

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“…Equol, which is a metabolite of daidzein, induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells through the intrinsic and endoplasmic reticulum stress pathways (26). Caspase-9 and the Bcl-2/Bax ratio are commonly used activity markers of the mitochondrial apoptotic pathway (43)(44)(45). In the present study, western blotting was used to detect these markers, revealing that the cleavage of caspase-9 increased and the ratio of Bcl-2/Bax decreased in both cell lines in a dose-dependent manner, which indicated that daidzein-induced apoptosis was mediated via the mitochondrial apoptotic pathway.…”

Section: Discussionmentioning

confidence: 99%

Daidzein induces choriocarcinoma cell apoptosis in a dose-dependent manner via the mitochondrial apoptotic pathway

Zheng

Sun

et al. 2018

Mol Med Report

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Choriocarcinoma is a malignant gestational trophoblastic disease and relapse or drug resistance occurs in ~25% of gestational trophoblastic tumors. Cell apoptosis serves a role in the progression from hydatidiform mole to persistent gestational trophoblastic disease. It has been demonstrated that daidzein [7‑hydroxy‑3‑(4‑hydroxyphenyl)‑4H‑chromen‑4‑one] may induce apoptosis in a number of cancer types via the mitochondrial apoptotic pathway by altering the B‑cell lymphoma (Bcl)‑2/Bcl‑2 associated X, apoptosis regulator (Bax) ratio, and activating the caspase cascade. Daidzein also serves a role in regulation of production of human chorionic gonadotropin in trophoblast cells and inhibition of cell proliferation. However, few reports have been published regarding the effect of daidzein on apoptosis in choriocarcinoma. Therefore, in the present study, JAR and JEG‑3 human gestational choriocarcinoma cells were used to investigate the effect of daidzein on apoptosis of choriocarcinoma cells. Treatment with daidzein for 48 h reduced cell viability in a dose‑dependent manner. The percentages of early and late apoptotic cells also increased following treatment with daidzein in a dose‑dependent manner, with the number of late apoptotic cells increasing more prominently. Furthermore, treatment with daidzein led to apoptosis‑associated alterations in nuclear morphology of JAR and JEG-3 cells. Expression levels of cleaved poly(ADP‑ribose) polymerase, cleaved caspase‑3 and cleaved caspase‑9 increased following treatment with daidzein, whereas the Bcl‑2/Bax ratio decreased in a dose‑dependent manner. In conclusion, the results of the present study demonstrate that daidzein may induce apoptosis of choriocarcinoma cells in a dose‑dependent manner via the mitochondrial apoptotic pathway.

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“…Oxymatrine (OMT) is an alkaloid derived from extract of Sophora flavescens and Sophora alopecuroides, which is a traditional Chinese medicine with anti-tumor [ 8 , 9 ], anti-inflammatory [ 10 ], and attenuating heart failure properties [ 11 ]. OMT is widely applied for various human diseases such as hepatitis B infection and liver fibrosis [ 12 ], and provides protection from damage to the liver, intestines, and heart [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine Inhibits Transforming Growth Factor β1 (TGF-β1)-Induced Cardiac Fibroblast-to-Myofibroblast Transformation (FMT) by Mediating the Notch Signaling Pathway In Vitro

Zhao

Tao

et al. 2018

Med Sci Monit

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BackgroundOxymatrine, a component extracted from the traditional Chinese herb Sophora japonica (Sophora flavescens Ait.), has various pharmacological effects, especially on the cardiovascular system. However, its cardiac protection effects and the underlying mechanism are still poorly understood. In the present study, we investigated the inhibitory effect and mechanism of oxymatrine on cardiac fibrosis induced by TGF-β1.Material/MethodsCardiac fibroblasts were isolated and purified from neonatal rats. Immunocytochemical staining was used to identify the cells. MTT assay and immunofluorescence staining were used to assess cardiac fibroblasts proliferation and myofibroblasts transformation. Hematoxylin-eosin staining was performed to evaluate morphological changes of cardiac fibroblasts. The secretion of type I and III collagen was assessed by staining with picrosirius red and the hydroxyproline content was determined by colorimetric assay. Cardiac fibroblast migration was examined by scratch assay and DNA content was detected to analyze cell cycle distribution using flow cytometry. Western blot analysis was used to detect the protein expressions of Notch pathway-associated protein in cardiac fibroblasts.ResultsOxymatrine and Notch signaling pathway inhibitor DAPT could attenuated TGF-β1 induced the capacity of proliferation and migration increased in cardiac fibroblasts, as well as the secretion of collagen and hydroxyproline colorimetric content in medium. TGF-β1 induced the biomarker α-SMA of fibroblast-to-myofibroblast transformation (FMT), which was inhibited by oxymatrine and DAPT. Western blotting confirmed that oxymatrine blocked the activation of Notch induced by TGF-β1.ConclusionsOxymatrine is a potential inhibitor FMT induced by TGF-β1, which is at least in part mediated via inhibition of Notch signaling.

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Oxymatrine Promotes S-Phase Arrest and Inhibits Cell Proliferation of Human Breast Cancer Cells <i>in Vitro</i> through Mitochondria-Mediated Apoptosis

Cited by 26 publications

References 24 publications

Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells inï¿½vitro

Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cells inï¿½vitro

Daidzein induces choriocarcinoma cell apoptosis in a dose-dependent manner via the mitochondrial apoptotic pathway

Oxymatrine Inhibits Transforming Growth Factor β1 (TGF-β1)-Induced Cardiac Fibroblast-to-Myofibroblast Transformation (FMT) by Mediating the Notch Signaling Pathway In Vitro

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