Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2

Liang, Cheng; Zhang, Jia Kai; Shi, Zhijun; Liu, Bing; Shen, Chengchun; Tao, Hui

doi:10.1007/s00280-011-1699-4

Cited by 92 publications

(65 citation statements)

References 32 publications

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“…It has been demonstrated previously that matrine induces apoptosis in human osteosarcoma MG-63 cells (14); however, whether matrine induces autophagy in MG-63 cells remains unknown. The aim of the present study was to observe whether autophagy was induced by matrine, and to investigate the role of autophagy in the antitumor effects of matrine on human osteosarcoma MG-63 cells and its underlying mechanism.…”

Section: Introductionmentioning

confidence: 92%

Matrine-induced autophagy counteracts cell apoptosis via the ERK signaling pathway in osteosarcoma cells

Huang

Guo

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to observe whether autophagy was induced by matrine, and to investigate the role of autophagy in the antitumor effects of matrine on human osteosarcoma MG-63 cells and its underlying mechanism. MG-63 cells were cultured in vitro in matrine at a concentration of 0.6, 0.8, 1.0 and 1.2 g/l for 0, 24, 48 and 72 h. A MTT assay was used to evaluate the proliferation inhibition of MG-63 cells by matrine, and Annexin V-fluorescein isothiocyanate/propidum iodide (PI) staining flow cytometry was used to analyze the apoptotic rate. Alterations in cell morphology was assessed by PI and Hoechst 33258 cell staining. Matrine-induced autophagy in MG-63 cells was confirmed by green fluorescent protein-microtubule-associated protein 1-light chain 3 (LC3) b transfection and fluorescence microscopy, and cell viability was investigated by MTT assay following inhibition of autophagy by chloroquine (CQ) pretreatment. The expression level of apoptosis-associated proteins B-cell lymphoma-2 (Bcl-2) and Bcl-2-like protein 4 (Bax), autophagy-associated LC3II protein, and the activation of extracellular signal-regulated kinase (ERK) was detected by western blotting. Cell proliferation was clearly inhibited by matrine in a dose-and time-dependent manner. Flow cytometry and Hoechst 33258/PI staining verified that matrine induced apoptosis in a time-dependent manner when cells were exposed to 1.1 g/l matrine; fluorescence microscopy demonstrated that green fluorescence puncta were enhanced with prolonged time of matrine incubation. Western blotting confirmed that the expression of pro-apoptosis-associated proteins Bax and LC3II, and phosphorylated-ERK were upregulated, and anti-apoptosis protein Bcl-2 was downregulated in a time-dependent manner following treatment with matrine.The cell viability of the matrine + CQ group was increased compared with the matrine group alone, which revealed that matrine treatment alone induced protective autophagy in MG-63 cells. In addiiton, expression of LC3II/LC3I decreased and the expression of BAX/Bcl-2 increased in the matrine + U0126 group compared with the matrine alone group. The present study demonstrated, to the best of our knowledge, for the first time that matrine induced protective autophagy via ERK activation in MG-63 cells, and matrine combined treatment with CQ or U0126 led to an increase in apoptosis in osteosarcoma cells.

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Section: Introductionmentioning

confidence: 92%

Matrine-induced autophagy counteracts cell apoptosis via the ERK signaling pathway in osteosarcoma cells

Huang

Guo

et al. 2016

Oncology Letters

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“…In the past few years, a growing body of evidence suggests that matrine and oxymatrine may have some promising potential in cancer treatment as demonstrated by their tumoricidal effects on many cancer cell lines including those derived from gastric cancer, cervical cancer, leukemia, hepatocellular carcinoma, breast cancer, pancreatic cancer and lung cancer (3,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The major mechanisms that have been postulated to underlie the antitumor effects of matrine center on the regulation of apoptosis-and proliferation-related genes and proteins, such as Bcl-2 family members, caspases, E2F-1, Akt and Fas/FasL (23,(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Matrine induces the apoptosis of lung cancer cells through downregulation of inhibitor of apoptosis proteins and the Akt signaling pathway

Huang

Zhang

et al. 2014

Oncology Reports

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Abstract. Lung cancer is the leading cause of cancer-related mortality in humans. The prognosis for advanced lung cancer patients is extremely poor. Current standard care is rather ineffective for prolonging patient life while preserving satisfactory quality of life due to adverse side-effects. Matrine extracted from the traditional Chinese herbal plant Sophora flavescens was shown to induce cancer cell death in vitro. The aim of this study was to investigate the effect of matrine on the proliferation and apoptosis of lung cancer cells and the molecular basis of matrine-induced apoptosis. The results showed that matrine inhibited cell proliferation and induced apoptosis in lung cancer A549 and 95D cells in a dose-and time-dependent manner. The apoptotic effects of matrine on lung cancer cells appeared to act via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway and downregulation of the expression of the inhibitor of apoptosis protein (IAP) family proteins. Matrine exerts its cancer-killing effect via promoting apoptosis in lung cancer cells and may be a useful adjuvant therapeutic scheme for treating advanced lung cancer patients.

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“…Approximately 5 · 10 6 MNNG/HOS cells were injected subcutaneously into the right axillary fossa of each nude mouse under aseptic conditions as described previously. 22 The next day (day 1) mice were randomly divided into three groups (n = 6) and fed plain drinking water (control), or 0.3% and 1% GA w/v in drinking water. Diet and water consumption as well as animal body weight were monitored regularly throughout the study.…”

Section: Xenograft Modelmentioning

confidence: 99%

Gallic Acid Induces the Apoptosis of Human Osteosarcoma Cells In Vitro and In Vivo via the Regulation of Mitogen-Activated Protein Kinase Pathways

Liang

Zhang

et al. 2012

Cancer Biotherapy and Radiopharmaceuticals

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To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase ( JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.

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Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2

Cited by 92 publications

References 32 publications

Matrine-induced autophagy counteracts cell apoptosis via the ERK signaling pathway in osteosarcoma cells

Matrine-induced autophagy counteracts cell apoptosis via the ERK signaling pathway in osteosarcoma cells

Matrine induces the apoptosis of lung cancer cells through downregulation of inhibitor of apoptosis proteins and the Akt signaling pathway

Gallic Acid Induces the Apoptosis of Human Osteosarcoma Cells In Vitro and In Vivo via the Regulation of Mitogen-Activated Protein Kinase Pathways

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