Oleanolic Acid Suppresses Migration and Invasion of Malignant Glioma Cells by Inactivating MAPK/ERK Signaling Pathway

Guo, Guocai; Yao, Weicheng; Zhang, Quanqin; Bo, Yongli

doi:10.1371/journal.pone.0072079

Cited by 80 publications

(62 citation statements)

References 23 publications

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“…Inhibition of MMPs could significantly reduce tumor invasion ability [24,25]. Cadherin is a kind of mucoprotein, which could mediate cell adhesion to extracellular matrix and promote cell metastasis [26,27]. Twist is an oncogene, which could inhibit apoptosis, modulate hypoxia metabolism, and induce epithelial-mesenchymal transition [28].…”

Section: Discussionmentioning

confidence: 99%

Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment

Cui

Song

et al. 2015

ABBS

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Glioma which has strong proliferation and angiogenesis ability is the most common and malignant primary tumor in central nervous system. Pituitary tumor transforming gene (PTTG) is found in pituitary tumor, and plays important role in cell proliferation, cell cycle, cell apoptosis, and angiogenesis. However, the role of PTTG in glioma is still incompletely investigated. Here, we explored the correlation between PTTG and glioma grade, as well as micro-vessel density (MVD). In addition, siRNA was used to silence PTTG expression in glioma cell lines including U87MG, U251, and SHG44. Cell proliferation, apoptosis, invasion, and angiogenesis were studied both in vitro and in vivo. Our results demonstrated that PTTG expression was significantly up-regulated in glioma, and had positive correlation with glioma grade and MVD. Silencing of PTTG inhibited glioma cell proliferation, migration/invasion, and angiogenesis, induced cell apoptosis, suppressed cell invasion, and arrested cell cycle at G0/G1 stage. Silencing of PTTG could also inhibit tumor growth, invasion, and angiogenesis in vivo. Our data indicated that PTTG might be a potential target for glioma treatment.

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Section: Discussionmentioning

confidence: 99%

Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment

Cui

Song

et al. 2015

ABBS

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“…It has been reported that the MAPK pathway is highly activated in many cancers, including glioma 17,24 . Our study further revealed the potential function of MEK2 in the chemotherapy resistance of gliomas.…”

Section: Discussionmentioning

confidence: 99%

MEK2 is a prognostic marker and potential chemo-sensitizing target for glioma patients undergoing temozolomide treatment

Yao

Zhang

et al. 2015

Cell Mol Immunol

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Although temozolomide (TMZ) is the first-line chemotherapeutic agent for glioblastoma, it is often non-curative due to drug resistance. To overcome the resistance of glioblastoma cells to TMZ, it is imperative to identify prognostic markers for outcome prediction and to develop chemo-sensitizing agents. Here, the gene expression profiles of TMZ-resistant and TMZ-sensitive samples were compared by microarray analysis, and mitogen-activated protein kinase kinase 2 (MEK2) was upregulated specifically in resistant glioma cells but not in sensitive tumor cells or non-tumor tissues. Moreover, a comprehensive analysis of patient data revealed that the increased level of MEK2 expression correlated well with the advancement of glioma grade and worse prognosis in response to TMZ treatment. Furthermore, reducing the level of MEK2 in U251 glioma cell lines or xenografted glioma models through shRNA-mediated gene knockdown inhibited cell proliferation and enhanced the sensitivity of cells toward TMZ treatment. Further analysis of tumor samples from glioma patients by real-time PCR indicated that an increased MEK2 expression level was closely associated with the activation of many drug resistance genes. Finally, these resistance genes were downregulated after MEK2 was silenced in vitro, suggesting that the mechanism of MEK2-induced chemo-resistance could be mediated by the transcriptional activation of these resistance genes. Collectively, our data indicated that the expression level of MEK2 could serve as a prognostic marker for glioma chemotherapy and that MEK2 antagonists can be used as chemo-sensitizers to enhance the treatment efficacy of TMZ.

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“…Moreover, it was reported that OA induces a concentration-dependent S phase and G2/M phase cell cycle arrest in Panc-28 and Hep-G2 cells [24,25]. The inhibitory effects of OA are due to the suppression of specific intracellular signaling pathways, such as the STAT3, JNK, AKT, and NF-kappaB signaling pathways [26] These studies indicate that OA can be proposed as an adjunct to cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 94%

Oleanolic Acid Induces p53 Dependent Apoptosis via the ERK/JNK/AKT Pathway in Cancer Cell Lines

Kim¹,

Jo²,

Chung³

et al. 2017

Preprint

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We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), and U87 (human glioblastoma) cells. The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA (at 100 µg/mL) increased the number of apoptotic cells to 27.0% in DU145, 27.0% in MCF-7, and 15.7% in U87 cells, when compared to control cells. This enhanced apoptosis was due to increases in p53, cytochrome c, and Bax expression. OA-treated DU145 cells were arrested in G2 because of the activation of p-ERK and p21, and the decrease in cyclin B1 and cyclin E expression. Furthermore, OA-treated MCF-7 cells were arrested in G1 owing to the activation of p-JNK, p-ERK, p21, and p27, and the decrease in p-AKT, cyclin E, and CDK2. U87 cells also exhibited G1 phase arrest caused by the increase in p-ERK, p-JNK, p21, and p27, and the decrease in CDK2. Thus, OA arrests the cell cycle in different phases, and increases apoptosis in cancer cells. These results suggest that OA may alter the expression of cell cycle regulatory proteins in a cancer type-dependent manner.

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Oleanolic Acid Suppresses Migration and Invasion of Malignant Glioma Cells by Inactivating MAPK/ERK Signaling Pathway

Cited by 80 publications

References 23 publications

Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment

Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment

MEK2 is a prognostic marker and potential chemo-sensitizing target for glioma patients undergoing temozolomide treatment

Oleanolic Acid Induces p53 Dependent Apoptosis via the ERK/JNK/AKT Pathway in Cancer Cell Lines

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