Matrine-Induced Apoptosis in Leukemia U937 Cells: Involvement of Caspases Activation and MAPK-Independent Pathways

Center for Molecular Biology, School of Medicine, Shantou University, Shantou, P. R. China.
Planta Medica (Impact Factor: 2.15). 06/2006; 72(6):501-6. DOI: 10.1055/s-2006-931534
Source: PubMed


It is reported that matrine, one of the major effective compounds isolated from the root of Sophora flavescens Ait., has anti-leukemia activity. In this study, we find that the treatment of leukemia U937 cells with matrine results in induction of apoptosis. Analysis of the mechanism underling this apoptotic event showed activation of caspases-9, -3, and -7, and release of cytochrome C from mitochondria to cytosol, and cleavage of poly(ADP-ribose) polymerase. Matrine did not alter the level of bcl-2 and bcl-xL as well as bax. In addition, no correlation was found between matrine administration and activation of the three major MAPK subfamilies (Erk1/2, p38, JNK/SAPK). The results indicate that matrine induces apoptosis in U937 cells via a cytochrome C-triggered caspase activation pathway.

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    • "The discovery of matrine as a novel Akt inhibitor may have implications for cancer biology and treatment. In addition, we have demonstrated that matrine inactivates the phosphorylation of ERK1/2 in NB4, U937, and primary AML cells during matrine-induced apoptosis, which differ from the previous report [19]. Liu et al [19] showed that the expression levels of p-ERK1/2 had no change at 48 h after treatment with 0.4 g/L matrine in U937 cells. "
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    ABSTRACT: Acute myeloid leukemia (AML) is a hematological malignancy characterized by a rapid increase in the number of immature myeloid cells in bone marrow. Despite recent advances in the treatment, AML remains an incurable disease. Matrine, a major component extracted from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines. However, the effects of matrine on AML remain largely unknown. Here we investigated its anticancer effects and underlying mechanisms on human AML cells in vitro and in vivo. The results showed that matrine inhibited cell viability and induced cell apoptosis in AML cell lines as well as primary AML cells from patients with AML in a dose- and time-dependent manner. Matrine induced apoptosis by collapsing the mitochondrial membrane potential, inducing cytochrome c release from mitochondria, reducing the ratio of Bcl-2/Bax, increasing activation of caspase-3, and decreasing the levels of p-Akt and p-ERK1/2. The apoptotic effects of matrine on AML cells were partially blocked by a caspase-3 inhibitor Z-DEVD-FMK and a PI3K/Akt activator IGF-1, respectively. Matrine potently inhibited in vivo tumor growth following subcutaneous inoculation of HL-60 cells in SCID mice. These findings indicate that matrine can inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective candidate as chemotherapeutic agent against AML.
    PLoS ONE 10/2012; 7(10):e46853. DOI:10.1371/journal.pone.0046853 · 3.23 Impact Factor
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    • "Matrine can also inhibit the invasiveness and metastasis of the human malignant melanoma cell line A375 and cervical cancer HeLa cells, as well as induce differentiation of leukemia K-562 cells [64–66]. In addition, matrine-induced autophagy in rat C6 glioma cells has been observed by electron microscopy [67]. "
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    ABSTRACT: To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As) and kushen flavonoids (KS-Fs) are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.
    Evidence-based Complementary and Alternative Medicine 08/2012; 2012:373219. DOI:10.1155/2012/373219 · 1.88 Impact Factor
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    • "Matrine, one of the main active components from the dry roots of Sophora flavescence (SF), has long been used for treatment of cancer, viral hepatitis, arrhythmia and skin diseases in China (Zhang and Huang, 2004). Some studies indicated that Matrine could induce leukemia U937, JM, K562 cells apoptosis and cell cycle arrest in vitro (Liu et al., 2006; Feng et al., 2003; Zhang et al., 2001). However, the mechanism of underlying the apoptotic process by Matrine remains to be elucidated. "
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    ABSTRACT: Matrine, one of the main active components from the dry roots of Sophora flavescence, was known to induce apoptosis in a variety of tumor cells in vitro. However, the molecular mechanism of cell apoptosis induced by Matrine remains elusive. Here, we investigated the apoptosis in Matrine-treated human gastric cancer MKN45 cells. The results showed that Matrine could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. Further immunoblots revealed that in Matrine-treated cells, caspase-3, -7 were activated and the pro-apoptotic molecules Bok, Bak, Bax, Puma, and Bim were also up-regulated. Our results suggested that Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family.
    Toxicology 02/2007; 229(3):245-52. DOI:10.1016/j.tox.2006.10.020 · 3.62 Impact Factor
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