Matrine induces apoptosis of human multiple myeloma cells via activation of the mitochondrial pathway
Laboratory of Internal Medicine, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China. Leukemia & lymphoma
(Impact Factor: 2.89).
07/2010; 51(7):1337-46. DOI: 10.3109/10428194.2010.488708
Multiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled proliferation of clonal plasma cells in bone marrow in the elderly. Although there have been tremendous advances in the treatment of MM, it remains an incurable disease. Matrine, a main alkaloid of the traditional Chinese herb Sophora flavescens Ait, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of matrine as a novel therapeutic agent for patients with MM. We investigated the effects of matrine for its anti-myeloma activity in vitro, and further examined the mechanisms of apoptosis induced by matrine. Matrine inhibited the proliferation of human myeloma cell lines as well as freshly isolated myeloma cells from patients in a dose- and time-dependent manner. Matrine showed a potent induction of apoptosis of myeloma cells. Mitochondrial membrane potential (Deltapsim) was lost and cytochrome c (cyt c) was released from mitochondria to cytosol in myeloma cells treated by matrine for 24 h in a dose-dependent manner. The ratio of Bcl-2/Bax protein decreased, and the percentage of activated caspase-3 increased in myeloma cells treated by matrine for 48 h, but this matrine-induced activity of caspase-3 was completely canceled by the addition of Z-Asp(O-Me)-Glu(O-Me)-Val-Asp(O-Me) fluoromethyl ketone (Z-DEVD-FMK), a caspase-3 inhibitor. The addition of Z-DEVD-FMK partially blocked the apoptotic effect of matrine on myeloma cells. These data indicated that matrine could exert antiproliferative effects on myeloma cells and induce apoptosis of myeloma cells in vitro. The induction of apoptosis appeared to proceed via the mitochondrial pathway, including down-regulation of Bcl-2/Bax ratio, loss of Deltapsim, release of cyt c from mitochondria to cytosol, and activation of caspase-3. These findings support the view that matrine may be a useful candidate as a chemotherapeutic agent against MM.
Available from: si Zhang
- "Matrine has been found to exhibit many biological activities, such as anti-inflammation, anti-virus, anti-fibrosis, anti-arrhythmia, and immunosuppression, leading to wide clinical use in the treatment of viral hepatitis, liver fibrosis, heart arrhythmia and skin diseases in China –. Recently, intensive studies have shown that matrine possesses potent antitumor activities by inhibiting proliferation and inducing apoptosis of cells from gastric cancer, lung cancer, hepatocellular carcinoma, breast cancer, melanoma, leukemia, multiple myeloma –. In addition, matrine can also induce the differentiation of leukemia K562 cells , the migration of lung cancer A549 cells , or the invasion of breast cancer MDA-MB-231 cells . "
[Show abstract] [Hide abstract]
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
[Show abstract] [Hide abstract]
ABSTRACT: In this paper we present Myanmar character identification of handwriting between exhibits and specimen of Myanmar handwriting documents. This is also a method to identify the writer of Myanmar handwriting documents. Many methods have been reported for handwriting-based writer identification. Most such techniques assume that the written text is fixed. There are many methods for writer identification. In our method, we take the handwriting as an image containing some special individual character features, and writer identification is regarded as individual character identification. We apply the fast Fourier transform (FFT) method to extract features for one character. In individual character, there are character features mingled with noises. We use median filter algorithm to remove noises in this individual character features. All features were appropriately binarized so that binary feature vectors of constant lengths could be fanned. We also evaluate a weighted euclidean distance (WED) to compare training character features for fulfil identification task. The result of this paper will confirm whether the handwriting of the specimen is the true writer of the exhibit. The current application domain of the framework is writer identification and handwriting examination as frequently used in crime investigation and prosecution. The method is tested on 40 writers and proves to give interesting result. The identification correct rate is 97.5% in our experiments
Information and Telecommunication Technologies, 2005. APSITT 2005 Proceedings. 6th Asia-Pacific Symposium on; 12/2005
[Show abstract] [Hide abstract]
ABSTRACT: Matrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has potent anti-tumor activity in various cancer cell lines. However, the activity of matrine against osteosarcoma remains unclear. In the present study, we examined the effects of matrine on human osteosarcoma cells and explored the underlying mechanism.
Four human osteosarcoma cell lines: MG-63, U-2OS, Saos-2, and MNNG/HOS were treated by matrine and subjected to MTT assay, annexin V-FITC/PI double staining, and TUNEL assay. The activation of caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined by qRT-PCR and Western blot. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered to evaluate the anti-cancer capacity of matrine in vivo.
We found that matrine inhibited the proliferation and induced apoptosis of the four osteosarcoma cell lines in vitro and induced the activation of caspase-3, -8, and -9 in a dose-dependent manner. Furthermore, the pro-apoptotic factors Bax and Fas/FasL were upregulated, and the anti-apoptotic Bcl-2 was downregulated. More importantly our in vivo, studies showed that administration of matrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of Bcl-2 and upregulation of Bax and Fas/FasL in MNNG/HOS tumor tissues following matrine treatment, consistent with the in vitro results.
Our results demonstrate that matrine inhibits the proliferation and induces apoptosis of human osteosarcoma cells in vitro and in vivo. The induction of apoptosis appears to occur through the upregulation of Fas/FasL and Bax, downregulation of Bcl-2, and activation of caspase-3, -8, and -9, which then trigger major apoptotic cascades.
Cancer Chemotherapy and Pharmacology 06/2011; 69(2):317-31. DOI:10.1007/s00280-011-1699-4 · 2.77 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.