Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by targeting the PI3K/AKT/mTOR signaling pathway

Liu, Ming; Wang, Jiwei; Qi, Qichao; Huang, Bin; Chen, Anjing; Li, Xingang; Wang, Jian

doi:10.3892/or.2016.4998

Cited by 25 publications

(16 citation statements)

References 26 publications

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“…Aberrant activation of the PI3K/AKT pathway has been widely reported in various cancers types during progression, including glioma (20)(21)(22). The PI3K/AKT pathway has roles in the cell proliferation, cell cycle progression and apoptosis resistance of glioma cells via its downstream targets, which include mTOR, Bcl-2, Bax, cyclin D1 and Bcl-2-like 1 (20,(23)(24)(25)(26). mTOR was reported to have an essential role in the cell survival, proliferation and apoptosis of glioma cells (27,28).…”

Section: Discussionmentioning

confidence: 99%

Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway

Zhang

Liu

et al. 2017

Mol Med Report

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Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival‑enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database. Furthermore, western blotting experiments were performed in U251 and U87 glioma cells, and Ngb knockdown using short hairpin RNA reduced the protein levels of phosphorylated (p)‑AKT, p‑mammalian target of rapamycin (mTOR) and antiapoptotic factor Bcl‑2, and increased the expression of the proapoptotic protein Bcl‑2‑associated X, in U251 cells. In addition, Ngb overexpression promoted the activation of the PI3K/AKT pathway in U87 cells. MK2206, a PI3K/AKT signaling inhibitor, reduced the expression of p‑AKT and increased the levels of apoptosis‑associated proteins, including cleaved poly(ADP‑ribose) polymerase 1 and cleaved caspase‑3/7/8, in Ngb‑overexpressing U87 cells. Furthermore, MK2206 treatment reduced the proliferation and induced the apoptosis of Ngb‑overexpressing U87 cells, as indicated by the results of MTT, colony formation and flow cytometry assays. In addition, insulin‑like growth factor‑1, a PI3K/AKT signaling activator, reversed Ngb knockdown‑induced growth arrest and apoptosis in U251 cells. In conclusion, the results of the present study indicate that Ngb may facilitate a malignant phenotype of glioma cells by activating the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway

Zhang

Liu

et al. 2017

Mol Med Report

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“…The PI3K/AKT/mTOR pathway is an important target due to its regulatory role in various cancers [24, 56, 57]; it is also involved in the invasion and metastasis and progression of hepatocellular carcinoma, cervical cancer, and LC [22, 25, 58]. ERS shares a correlation with the PI3K/Akt/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

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“…Due to that GBM is highly proliferative, invasive and chemoresistant, the combined treatments of surgery, chemotherapy, and radiotherapy have not significantly improved the survival rate of GBM patients [46,47]. Liu et al dissected that NC impaired cell viability and motility of GMB cells via inactivation of pAkt and mTOR [48]. Moreover, NC was reported to increase the expression of cleaved PARP and cleaved caspase 3, and to inhibit pDok2 in GBM cells [49].…”

Section: Glioblastomamentioning

confidence: 99%

Antitumor functions and mechanisms of nitidine chloride in human cancers

Cui¹,

Wu²,

Cao³

et al. 2020

J. Cancer

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Nitidine chloride (NC), a quaternary ammonium alkaloid, exhibits multiple biological activities, including antimalarial, antifungal, and antiangiogenesis. Recently, NC has been characterized to perform antitumor activity in a variety of malignancies. NC has been identified to suppress cell proliferation, stimulate apoptosis, and induce cell cycle arrest, retard migration, invasion and metastasis. Moreover, NC is reported to sensitize cancer cells to chemotherapeutic drugs. In this review article, we describe the functions of NC in human cancers and discuss the molecular insight into NC-involved antitumor feature. This review article will stimulate the deeper investigation for using NC as a potent agent for the management of cancer patients.

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Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by targeting the PI3K/AKT/mTOR signaling pathway

Cited by 25 publications

References 26 publications

Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway

Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Antitumor functions and mechanisms of nitidine chloride in human cancers

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