Matrine Induces Apoptosis in Gastric Carcinoma Cells via Alteration of Fas/FasL and Activation of Caspase-3

Department of Oncology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xiwu Road 157#, Xi'an 710004, Shaanxi province, PR China.
Journal of ethnopharmacology (Impact Factor: 3). 06/2009; 123(1):91-6. DOI: 10.1016/j.jep.2009.02.022
Source: PubMed


Matrine, an alkaloid purified from the chinese herb Sophora flavescens Ait, is well known to possess activities including anti-inflammation, anti-fibrotic and anticancer. In this study, the mechanism of matrine inducing the apoptosis of gastric carcinoma cells was investigated.
Proliferation of SGC-7901 cells was examined by MTT assay. Cellular morphology was observed under transmission electron microscope. Flow cytometry (FCM) was used to observe the apoptosis of SGC-7901 cells by staining with annexinV-FITC/PI. The expression levels of Fas/FasL in SGC-7901 cells were monitored by FCM analysis using an indirect immunofluorescence method. Activity of caspase-3 enzyme was measured by spectrofluorometry.
MTT assay showed that matrine inhibited SGC-7901 cells proliferation in a dose-dependent and time-dependent manner. Apoptosis induction was demonstrated by morphological changes under electron microscope and FCM analysis. Fluorescence intensity levels of Fas and FasL were found to be equally up-regulated after matrine treatment, which were both correlated with apoptosis rate. The activity of caspase-3 enzyme increased in matrine groups, positively correlated with apoptosis rate.
Matrine could inhibit cell proliferation and induce apoptosis of SGC-7901 cells in vitro. The apoptosis induction appears to proceed by up-regulating Fas/FasL expression and activating caspase-3 enzyme.

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    • "Matrine, an alkaloid isolated from the root of Sophora subprostrata, is originally used in the treatment of enteritis, hepatitis, hepatic fibrosis and hypertension in China [5]. Matrine is also found to induce cell death in many kinds of cancer cells, including cervical cancer, leukemia, gastric cancer, lung cancer and breast cancer [6-10], and thus is considered as a promising drug for cancer therapy. "
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    ABSTRACT: Matrine, a clinical drug in China, has been used to treat viral hepatitis, cardiac arrhythmia and skin inflammations. Matrine also exhibits chemotherapeutic potential through its ability to trigger cancer cell death. However, the mechanisms involved are still largely unknown. The objective of this study was to investigate the major determinant for the cell death induced by matrine in human hepatocellular carcinoma. We use human hepatocellular carcinoma cell line HepG2 and human hepatocellular carcinoma xenograft in nude mice as models to study the action of matrine in hepatocellular cancers. We found that caspase-dependent and -independent Program Cell Death (PCD) occurred in matrine-treated HepG2 cells, accompanied by the decreasing of mitochondrial transmembrane potential and the increasing ROS production. Further studies showed that AIF released from the mitochondria to the nucleus, and silencing of AIF reduced the caspase-independent PCD induced by matrine. What's more, AIF nuclear translocation, and the subsequent cell death as well, was prevented by Bid inhibitor BI-6C9, Bid-targeted siRNA and ROS scavenger Tiron. In the in vivo study, matrine significantly attenuated tumor growth with AIF release from mitochondria into nucleus in nude mice. These data imply that matrine potently induce caspase-independent PCD in HepG2 cells through Bid-mediated AIF translocation.
    Molecular Cancer 03/2014; 13(1):59. DOI:10.1186/1476-4598-13-59 · 4.26 Impact Factor
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    • "Among the caspase family, caspase-3 has been widely studied, and has been proposed to have a crucial role in the cell death process (25,26). It has been shown that caspase-3 induces apoptosis through several different pathways, including degrading antiapoptotic proteins, and cleaving DNA repair molecules, extracellular matrix proteins, cytoskeletal proteins and other associated molecules (27). The results of the present study showed that expression of caspase-3 increased when Jurkat cells were treated with lidocaine, and that this was positively correlated with the rate of apoptosis. "
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    ABSTRACT: Lidocaine, as an anesthetic substance, is often used for surface and spinal anesthesia. However, studies have shown that lidocaine may induce transient neurological symptoms and cauda equina syndrome. In the present study the effects of the ginsenoside Rg1 (Rg1) on lidocaine‑induced apoptosis were assessed in Jurkat cells using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The data showed that incubation with Rg1 provides protection against lidocaine‑induced apoptosis in cultured Jurkat cells. In order to investigate the effect of Rg1 on the apoptosis pathway, caspase 3 gene expression was determined. The results suggested that the protective effect of Rg1 on lidocaine‑induced apoptosis is mediated by altering the level of B‑cell lymphoma‑2 (BCL‑2) family proteins and downregulating caspase‑3 expression. In conclusion, the present study demonstrated that incubation with Rg1 provides protection against lidocaine‑induced apoptosis in cultured Jurkat cells. In addition, the study demonstrated that Rg1 is a notable antiapoptotic molecule that is capable of blocking the caspase‑dependent signaling cascade in Jurkat cells, and that the protective effect of Rg1 on lidocaine‑induced apoptosis is mediated by altering levels of BCL‑2 family proteins and downregulating caspase‑3 expression. The present study provides the basis for understanding and evaluating the effect of Rg1 in the in vivo treatment of lidocaine-induced transient neurological symptoms and cauda equina syndrome by lidocaine.
    Molecular Medicine Reports 11/2013; 9(2). DOI:10.3892/mmr.2013.1822 · 1.55 Impact Factor
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    • "Fas ligand (FasL) is a type II transmembrane protein and signals through trimerization of FasR, which spans the membrane of the “target” cell. This trimerization usually leads to apoptosis, or cell death [13]. "
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    ABSTRACT: Background β-elemene, a natural sesquiterpene extracted from the essential oils of Curcuma aromatica Salisb, has been shown to be effective against a wide range of tumors. In this study, the antitumor effect of β-elemene on a human hepatoma cell line, HepG2, and the mechanism involved have been investigated. Methods MTT assay was used to determine the growth inhibition of hepatoma HepG2 cells in vitro. Apoptosis of HepG2 cells were demonstrated by fluorescence microscope with Hoechst 33258 staining and flow cytometry with Annexin V-FITC/PI double staining. Flow cytometry was performed to analyze the cell cycle distribution of HepG2 cells. The mRNA and protein expression of Fas and FasL were measured by RT-PCR and Western blot analysis. Results MTT results showed that β-elemene could inhibit the proliferation of HepG2 cells in a time- and dose- dependent manner. Our results showed β-elemene had positive effect on apoptosis through fluorescence microscope and flow cytometry assay. Furthermore, β-elemene could induce the cell cycle arrest of the HepG2 cells in the G2/M phase. Fas and FasL expression were obviously increased after β-elemene treatment in both mRNA and protein level. Conclusion The present study indicates that β-elemene can effectively inhibit proliferation and induce apoptosis in hepatoma HepG2 cells, and the apoptosis induction is related with up-regulating of Fas/FasL expression.
    Cancer Cell International 03/2013; 13(1):27. DOI:10.1186/1475-2867-13-27 · 2.77 Impact Factor
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