Double Blockade of Glioma Cell Proliferation and Migration by Temozolomide Conjugated with NPPB, a Chloride Channel Blocker

Park, Miri; Song, Chi-Man; Yoon, Hojong; Choi, Kee‐Hyun

doi:10.1021/acschemneuro.5b00178

Cited by 16 publications

(11 citation statements)

References 45 publications

(78 reference statements)

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“…Malignant gliomas often recur within 1-2 cm of the original tumor site because of the tumor cell invasion into the surrounding normal brain tissue where they can evade surgical removal and radiation therapy. In view of this disadvantage of the current therapeutic method, efforts on exploring the reliable therapeutic targets based on identifying the molecular pathological process of gliomas, might provide a better cure and therapy for glioma (14) . In the present study, we confirmed the key role of Gli1-AQP1 signal pathway in glioma cell metastasis and survival.…”

Section: Discussionmentioning

confidence: 99%

Glioma-Associated Oncogene Homolog1 (Gli1)-Aquaporin1 pathway promotes glioma cell metastasis

Liao

et al. 2016

BMB Reports

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Glioma-Associated Oncogene Homolog1 (Gli1) is known to be activated in malignant glioma; however, its downstream pathway has not been fully explained. The aim of this study was to explore the role of Gli1-Aquaporin1 (AQP1) signal pathway in glioma cell survival. Our data suggests that both Gli1 and AQP1 are upregulated in glioma tissues, as in comparison to in normal tissues. These up-regulation phenomena were also observed in glioma U251 and U87 cells. It was demonstrated that Gli1 positively regulated the AQP1 expression. By luciferase reporter gene and ChIP assay, we observed that this modulation process was realized by combination of Gli1 with AQP1 promotor. In addition, knock down of Gli1 by siRNA interference reduced the viability of glioma cells as well as suppressed cell metastasis. Also, the inhibitory effects of cell survival by silenced Gli1 were abrogated by AQP1 overexpression. In summary, glioma cell survival is a regulatory process and can be mediated by Gli1-AQP1 pathway. [BMB Reports 2016; 49(7): 394-399]

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Section: Discussionmentioning

confidence: 99%

Glioma-Associated Oncogene Homolog1 (Gli1)-Aquaporin1 pathway promotes glioma cell metastasis

Liao

et al. 2016

BMB Reports

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“…The interesting conclusions drawn in this work were that no single compound in the Compound Kushing Injection mixture accounted for the full therapeutic effect of the whole extract; combinations of agents were required to reconstitute the beneficial activity, and the most effective combinations of compounds depended on the cancer cell type. Combined block of glioma cells with 5-nitro-2-(3-phenylpropylamino)-benzoate (a nonspecific chloride channel blocker), covalently linked to temozolomide (an oral chemotherapeutic drug for glioblastoma) suppressed glioma cell proliferation, migration, and invasion (Park et al, 2016). Temozolomide modifies DNA or RNA at guanine and adenine bases by addition of methyl groups (Lee, 2016); however, a substantial proportion of tumors are insensitive to temozolamide due to expression of methyltransferase genes.…”

Section: Pharmacological Targets For Cancer Treatmentmentioning

confidence: 99%

Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion

Yool

Ramesh

2020

Front. Pharmacol.

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The highly invasive nature of glioblastoma imposes poor prospects for patient survival. Molecular evidence indicates glioblastoma cells undergo an intriguing expansion of phenotypic properties to include neuron-like signaling using excitable membrane ion channels and synaptic proteins, augmenting survival and motility. Neurotransmitter receptors, membrane signaling, excitatory receptors, and Ca 2+ responses are important candidates for the design of customized treatments for cancers within the heterogeneous central nervous system. Relatively few published studies of glioblastoma multiforme (GBM) have evaluated pharmacological agents targeted to signaling pathways in limiting cancer cell motility. Transcriptomic analyses here identified classes of ion channels, ionotropic receptors, and synaptic proteins that are enriched in human glioblastoma biopsy samples. The pattern of GBM-enriched gene expression points to a major role for glutamate signaling. However, the predominant role of AMPA receptors in fast excitatory signaling throughout the central nervous system raises a challenge on how to target inhibitors selectively to cancer cells while maintaining tolerability. This review critically evaluates a panel of ligand-and voltage-gated ion channels and synaptic proteins upregulated in GBM, and the evidence for their potential roles in the pathological disease progress. Evidence suggests combinations of therapies could be more effective than single agents alone. Natural plant products used in traditional medicines for the treatment of glioblastoma contain flavonoids, terpenoids, polyphenols, epigallocatechin gallate, quinones, and saponins, which might serendipitously include agents that modulate some classes of signaling compounds highlighted in this review. New therapeutic strategies are likely to exploit evidence-based combinations of selected agents, each at a low dose, to create new cancer cell-specific therapeutics. A BFIGURE 1 | Illustration of a sample distribution of published glioblastoma studies suggesting less than 3% combine three themes (inhibitor, proliferation, motility). Venn diagram (A) summarizing the numbers of published articles on glioblastoma, with key words linked to inhibition,

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“…Thus, Cl À ions also play an important role in glioma cell migration and invasion. One of the voltage-gated chloride channel, CLC-3, encoded by the CLCN3 gene, has also been recognized as a crucial regulator of glioma cell migration and invasion by modulating cellular shape and volume (10,(20)(21)(22). CLC-3 is highly expressed on the plasma membrane of glioma cells compared with the normal brain.…”

Section: Ion Channels and Glioma Invasion/ Migrationmentioning

confidence: 99%

Ion Channels and Their Role in the Pathophysiology of Gliomas

Takayasu

Kurisu

Esquenazi

et al. 2020

Molecular Cancer Therapeutics

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Malignant gliomas are the most common primary central nervous system tumors and their prognosis is very poor. In recent years, ion channels have been demonstrated to play important roles in tumor pathophysiology such as regulation of gene expression, cell migration, and cell proliferation. In this review, we summarize the current knowledge on the role of ion channels on the development and progression of gliomas. Cell volume changes through the regulation of ion flux, accompanied by water flux, are essential for migration and invasion. Signaling pathways affected by ion channel activity play roles in cell survival and cell proliferation. Moreover, ion channels are involved in glioma-related seizures, sensitivity to chemotherapy, and tumor metabolism. Ion channels are potential targets for the treatment of these lethal tumors. Despite our increased understanding of the contributions of ion channels to glioma biology, this field remains poorly studied. This review summarizes the current literature on this important topic.

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Double Blockade of Glioma Cell Proliferation and Migration by Temozolomide Conjugated with NPPB, a Chloride Channel Blocker

Cited by 16 publications

References 45 publications

Glioma-Associated Oncogene Homolog1 (Gli1)-Aquaporin1 pathway promotes glioma cell metastasis

Glioma-Associated Oncogene Homolog1 (Gli1)-Aquaporin1 pathway promotes glioma cell metastasis

Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion

Ion Channels and Their Role in the Pathophysiology of Gliomas

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