Protective role of autophagy in matrine-induced gastric cancer cell death

Li, Yumin; Zhang, Junqiang; Ma, Haizhen; Chen, Xiaohui; Liu, Tao; Zhang, Jiao; He, Wenting; Wang, Furong; Liu, Xiaokang; Zeng, Xu

doi:10.3892/ijo.2013.1817

Cited by 38 publications

(33 citation statements)

References 74 publications

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“…This suggests that matrine-induced protective autophagy partially suppressed apoptosis of cells. The present results are in agreement with other studies, which demonstrate that inhibition of autophagy by 3-methyladenine and CQ significantly increases matrine-induced apoptosis (9,10).…”

Section: Discussionsupporting

confidence: 94%

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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: Discussionsupporting

confidence: 94%

“…It has been demonstrated that matrine exhibits a potent anti-tumor activity in various cancer cell lines, including breast cancer and leukemia (6)(7)(8). In addition, studies have revealed that matrine induces protective autophagy in hepatocellular and gastric cancer (9,10).…”

Section: Introductionmentioning

confidence: 99%

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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“…It's illustrated by these results that the autophagy induced by cisplatin is protective autophagy, some of which antagonize the apoptosis of gastric cancer cell, and chloroquine has the function of promoting cisplatin to induce apoptosis by inhibiting autophagy viability. It's similar to the research result on gastric cancer cell treated by 3-MA and matrine which was studied by Li et al (2013). It's also found that the expression of Caspase-3 and P53 is up-regulated in combined group, while the expression of apoptosis inhibiting protein Bcl-2 is down-regulated.…”

Section: Discussionsupporting

confidence: 72%

Autophagy Inhibition Sensitizes Cisplatin Cytotoxicity in Human Gastric Cancer Cell Line Sgc7901

Zhang¹,

Fang²,

Lu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)-induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells were treated with DDP and/or chloroquine, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; autophagy and apotosis-related proteins expression were detected by Western blot; and quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP for 24 h, the rates of cell apoptosis were (21.07±2.12)%. Autophagy, characterized by an increase in the number of autophagic vesicles and the level of LC3-II protein was observed in cells treated with DDP. After inhibition of autophagy by chloroquine, the rates of cell apoptosis were increased to (30.16±3.54)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2 protein was decreased. Therefore, autophagy protects human gastric cancer cell line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote apoptosis, and combination therapy with DDP and chloroquine may be a promising therapeutic strategy for gastric cancer.

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“…Matrine has been shown to produce a wide range of pharmacological effects and has been used to treat a variety of diseases, including viral hepatitis, neuropathic pain and isoproterenol-induced heart disease (11)(12)(13). In addition, significant antitumor effects have been found in gastric cancer, rhabdomyosarcoma, acute myeloid leukemia and breast cancer (14,15), and studies have shown that matrine exhibits antioxidant effects in a number of diseases. PD is mainly caused by damage to dopamine neurons, and oxidative stress is one of its important pathogenetic factors.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression

et al. 2016

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Abstract. The incidence rate of Parkinson's disease (PD) is ≤2% in Chinese individuals >65 years old, accounting for 40% of the global total of PD patients. The pathogenesis of PD is not yet clear, and oxidative stress-induced mitochondrial dysfunction is considered to be the main reason for the onset of PD. Studies have shown that matrine exhibits good antioxidant activity. Thus, the present study aimed to observe the protective effect and mechanism of matrine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuron damage. A total of 25 C57BL male mice were randomly divided into 5 groups, consisting of the control group (group A), the MPTP group (group B) and three matrine (4, 8 and 16 mg/kg) plus MPTP treatment groups (groups C, D and E, respectively). Results from a pole-climbing test and locomotor activity experiments were recorded. The mice were sacrificed 4 days later and brain dissection was performed. The levels of superoxide dismutase (SOD) and glutathione (GSH) were assessed. The expression level of tyrosine hydroxylase (TH) in the ventral midbrain was studied by immunofluorescence analysis. The expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) in the ventral midbrain was studied by western blot analysis. The experiments were repeated three times. Compared with control mice, the PD mice exhibited the typical behaviors associated with PD; matrine can alleviate this phenomenon, and with increasing matrine concentration, the symptoms were reduced significantly. Compared with the control mice, the PD mice had lower SOD and GSH activity, and matrine partially reversed the change in SOD and GSH activity. Immunofluorescence analysis showed that the level of TH in the ventral midbrain decreased significantly in the PD mice, and that the mice administered matrine showed higher expression of TH and levels of TH-positive cells. Western blotting results showed that the expression of Nrf2 in the ventral midbrain decreased significantly in the PD mice, and that matrine was able to reverse this phenomenon. In conclusion, by promoting antioxidant-related Nrf2 signaling pathways in the ventral midbrain, matrine can inhibit the oxidative damage of dopamine neurons in PD.

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Protective role of autophagy in matrine-induced gastric cancer cell death

Cited by 38 publications

References 74 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

Autophagy Inhibition Sensitizes Cisplatin Cytotoxicity in Human Gastric Cancer Cell Line Sgc7901

Neuroprotective effect of matrine on MPTP-induced Parkinson's disease and on Nrf2 expression

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