Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway

Jiang, Yan; Zhang, Qiuli; Bao, Jinsuo; Du, Chenghua; Wang, Jian; Tong, Qiang; Liu, Chang

doi:10.1016/j.biopha.2015.07.006

Cited by 29 publications

(17 citation statements)

References 22 publications

(25 reference statements)

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“…More and more studies have shown the potential therapeutic effect of S. Chinensis against cancer [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 18 , 19 , 20 , 21 ]. However, the underlying mechanisms have yet to be explained.…”

Section: Discussionmentioning

confidence: 99%

“…In China, S. chinensis is officially listed in the Chinese Pharmacopoeia as a tonic and used extensively for treating chronic or acute diseases including viral or chemical hepatitis, high cholesterol, hypertension, hyperglycaemia, and atherosclerosis [ 6 ]. In addition, S. chinensis supresses cell proliferation and induces apoptosis in several cancer cell lines including U251 and U87 glioma cells [ 7 ], human epithelial colorectal adenocarcinoma Caco-2 cells [ 8 ], U937 leukaemia cells [ 9 ], colon adenocarcinoma LoVo and ovarian adenocarcinoma 2008 cells [ 10 ], human colon cancer HCT116c cells [ 11 ], human colorectal carcinoma HT-29 cells [ 12 ], mouse melanoma B16F0 cells [ 13 ], and mouse breast cancer 4T1 cells [ 14 ]. Several reports have suggested that the major bioactive constituents of S. chinensis are the dibenzocyclooctadiene lignans schisandrin A, schisandrin B [ 15 ], gomisin A, gomisin N [ 16 ], essential oils [ 17 ], and polysaccharides [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

Chen

Shi

Wang

et al. 2016

IJMS

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According to the potential anti-hepatoma therapeutic effect of Schisandra chinensis polysaccharides presented in previous studies, a bioactive constituent, homogeneous Schisandra chinensis polysaccharide-0-1 (SCP-0-1), molecular weight (MW) circa 69.980 kDa, was isolated and purified. We assessed the efficacy of SCP-0-1 against human hepatocellular liver carcinoma (HepG2) cells to investigate the effects of its antitumour activity and molecular mechanisms. Anticancer activity was evaluated using microscopy, 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 staining, acridine orange (AO) staining, flow cytometry (FCM), and cell-cycle analysis. SCP-0-1 inhibited the HepG2 cells’ growth via inducing apoptosis and second gap/mitosis (G2/M) arrest dose-dependently, with a half maximal inhibitory concentration (IC50) value of 479.63 µg/mL. Western blotting of key proteins revealed the apoptotic and autophagic potential of SCP-0-1. Besides, SCP-0-1 upregulated Bcl-2 Associated X Protein (Bax) and downregulated B-cell leukemia/lymphoma 2 (Bcl-2) in the HepG2 cells. The expression of caspase-3, -8, and -9; poly (ADP-ribose) polymerase (PARP); cytochrome c (Cyt C); tumor protein 53 (p53); survivin; sequestosome 1 (p62); microtubule-associated protein 1 light chain-3B (LC3B); mitogen-activated protein kinase p38 (p38); extracellular regulated protein kinases (ERK); c-Jun N-terminal kinase (JNK); protein kinase B (AKT); and heat shock protein 90 (Hsp90) were evaluated using Western blotting. Our findings demonstrate a novel mechanism through which SCP-0-1 exerts its antiproliferative activity and induces mitochondrial apoptosis rather than autophagy. The induction of mitochondrial apoptosis was attributed to the inhibition of the Hsp90/AKT signalling pathway in an extracellular signal-regulated kinase-independent manner. The results also provide initial evidence on a molecular basis that SCP-0-1 can be used as an anti-hepatocellular carcinoma therapeutic agent in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

Chen

Shi

Wang

et al. 2016

IJMS

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show abstract

“…PI3K signaling increases glioblastomas formation and tumor progression in mouse-engineered models, launching PI3K and its effecter mTOR as convincing targets. mTOR incorporates oncogenic signaling from some growth factor receptors via PI3K, to modulate nutrient status and cellular energy, to stimulate downstream targets that promote tumor growth and suppress glioma cell invasion [22, 23]. The standard chemotherapy for GBM is temozolamide (TMZ) [24], an alkylation agent that leads to DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TELO2 decreases survival in human high-grade gliomas

et al. 2016

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High-grade gliomas are characterized with poor prognosis. To improve the clinical outcome, biomarker is urgently needed for distinguishing oncotarget in high-grade gliomas. Telomere maintenance 2 (TELO2) regulates S-phase checkpoint in cell cycle, and is involved in DNA repair. However, the role of TELO2 in survival outcome of high-grade gliomas is still not yet clarified. This study aims to investigate the correlation between TELO2 mRNA expression and survival outcome of patients with high-grade gliomas. Based on bioinformatics study, we found that Kaplan-Meier analysis demonstrated shorter survival in patients with higher TELO2 mRNA levels than in those with lower TELO2 expression (median survival, 59 vs. 113 weeks, p=0.0017, by log-rank test, hazard ratio: 0.3505, 95% CI: 01824.-0.6735). TELO2 mRNA expression significantly higher in World Health Organization (WHO) grade IV than in non-tumor control (p=2.85 × 10−9). Moreover, TELO2 level was greater in WHO grade III than in non-tumor controls (p= 0.017) human gliomas. We further validated TELO2 mRNA expression and protein levels by using quantitative RT-PCR, Western blot, and immunohistochemical (IHC) stain of tissue microarray. Consistently, the TELO2 mRNA and protein expression were significantly elevated in human glioma cells in comparison with normal brain control. Additionally, IHC staining showed higher TELO2 immunostain score in high-grade gliomas than in low-grade gliomas, or normal brain control. Taken together, human high-grade gliomas increase TELO2 mRNA expression, and overexpression of TELO2 mRNA expression correlates with shorter survival outcome, supporting that TELO2 is an oncotarget in human gliomas.

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“…It is therefore advantageous to utilize therapeutic strategies targeting MMP-9 expression. Negative regulation of MMP-9 expression has also been demonstrated to suppress metastatic activity of prostate cancer [71,72] malignant glioma [73] and renal cell carcinoma [74]. When Salmonella is used as an antitumor agent, it inhibits not only tumor vascularization [49], but also prevents EMT by keeping an intact ECM via suppression of MMP-9 expressions [50].…”

Section: Salmonella Diminishes Tumor Metastasismentioning

confidence: 99%

Salmonella-Based Targeted Cancer Therapy: Updates on A Promising and Innovative Tumor Immunotherapeutic Strategy

Pangilinan

Lee

2019

Biomedicines

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Presently, cancer is one of the leading causes of death in the world, primarily due to tumor heterogeneity associated with high-grade malignancy. Tumor heterogeneity poses a tremendous challenge, especially with the emergence of resistance not only to chemo- and radiation- therapies, but also to immunotherapy using monoclonal antibodies. The use of Salmonella, as a highly selective and penetrative antitumor agent, has shown convincing results, thus meriting further investigation. In this review, the mechanisms used by Salmonella in combating cancer are carefully explained. In essence, Salmonella overcomes the suppressive nature of the tumor microenvironment and coaxes the activation of tumor-specific immune cells to induce cell death by apoptosis and autophagy. Furthermore, Salmonella treatment suppresses tumor aggressive behavior via inhibition of angiogenesis and delay of metastatic activity. Thus, harnessing the natural potential of Salmonella in eliminating tumors will provide an avenue for the development of a promising micro-based therapeutic agent that could be further enhanced to address a wide range of tumor types.

show abstract

Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway

Cited by 29 publications

References 22 publications

A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells

Overexpression of TELO2 decreases survival in human high-grade gliomas

Salmonella-Based Targeted Cancer Therapy: Updates on A Promising and Innovative Tumor Immunotherapeutic Strategy

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