The Emerging Role of Voltage-Gated Sodium Channels in Tumor Biology

Mao, Weijia; Zhang, Jie; Körner, Heinrich; Jiang, Yong; Shi, Ying

doi:10.3389/fonc.2019.00124

Cited by 45 publications

(48 citation statements)

References 68 publications

(74 reference statements)

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“…Further examination using other methods is required. We focused on the sodium transport by SGLT2 because sodium uptake is emerging as a mechanism of cancer biology including breast cancer [15]. Ipragliflozin shut down sodium uptake through SGLT2 and induced membrane hyperpolarization of MCF-7 cells.…”

Section: Discussionmentioning

confidence: 99%

SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation

et al. 2020

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Cancer is currently one of the major causes of death in patients with type 2 diabetes mellitus. We previously reported the beneficial effects of the glucagon-like peptide-1 receptor agonist exendin-4 against prostate and breast cancer. In the present study, we examined the anti-cancer effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin using a breast cancer model. In human breast cancer MCF-7 cells, SGLT2 expression was detected using both RT-PCR and immunohistochemistry. Ipragliflozin at 1-50 μM significantly and dose-dependently suppressed the growth of MCF-7 cells. BrdU assay also revealed that ipragliflozin attenuated the proliferation of MCF-7 cells in a dose-dependent manner. Because the effect of ipragliflozin against breast cancer cells was completely canceled by knocking down SGLT2, ipragliflozin could act via inhibiting SGLT2. We next measured membrane potential and whole-cell current using the patch clamp technique. When we treated MCF-7 cells with ipragliflozin or glucose-free medium, membrane hyperpolarization was observed. In addition, glucose-free medium and knockdown of SGLT2 by siRNA suppressed the glucose-induced whole-cell current of MCF-7 cells, suggesting that ipragliflozin inhibits sodium and glucose cotransport through SGLT2. Furthermore, JC-1 green fluorescence was significantly increased by ipragliflozin, suggesting the change of mitochondrial membrane potential. These findings suggest that the SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation via membrane hyperpolarization and mitochondrial membrane instability.

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Section: Discussionmentioning

confidence: 99%

SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation

et al. 2020

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“…[47] Many thorough reviews already exist concerning VGSC, VGPC as well as voltage-gated calcium channels (VGCC) and the roles they play in cancer progression and altering the cell V m . [48][49][50]…”

Section: Ion Channelsmentioning

confidence: 99%

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Robinson

Jain

Sherman

et al. 2021

Advanced Therapeutics

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Bioelectronic medicine is a treatment modality that uses electricity to treat disease by altering the body's electrical communication systems. All cells are electrically active, in that they possess bioelectric circuitry generating a resting membrane potential and endogenous electric fields that influence cell functions and communication. There is now an accepted paradigm that cancer is characterized by malfunctions in cells' bioelectrical circuitry. This yields opportunities for bioelectronic medicine as novel treatments for cancer by manipulating its bioelectrical properties. To highlight the possibilities a bioelectrical approach can offer cancer therapy, the relevance of bioelectrical activity in cancer is reviewed and also how such activity can be hijacked in novel treatments. This includes sensing or measuring the electrical activity of cells for diagnostic and prognostic applications, controlling or altering bioelectricity including both ionic and faradaic current processes, and eliciting morphological changes using electric fields. Importantly, key links between cellular ionic and faradaic processes that contribute to cancer phenotypes are presented, which if considered and understood as a whole, can bring broad-reaching improvements to cancer therapy.

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“…In cancer, Na V expression is often upregulated, therefore inhibitors of Na V channels have been shown to decrease cancer cell invasion [259]. For example, Na V 1.1 and Na V 1.3 are highly expressed in ovarian cancer cells, while Na V 1.2 and Na V 1.4 are predominantly overexpressed in highly metastatic ovarian cancer cells compared to low-metastatic cells [260].…”

Section: Vgscs (Na V Channels)mentioning

confidence: 99%

Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance

Almasi

Hiani

2020

Cancers

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Improving the therapeutic efficacy of conventional anticancer drugs represents the best hope for cancer treatment. However, the shortage of druggable targets and the increasing development of anticancer drug resistance remain significant problems. Recently, membrane transport proteins have emerged as novel therapeutic targets for cancer treatment. These proteins are essential for a plethora of cell functions ranging from cell homeostasis to clinical drug toxicity. Furthermore, their association with carcinogenesis and chemoresistance has opened new vistas for pharmacology-based cancer research. This review provides a comprehensive update of our current knowledge on the functional expression profile of membrane transport proteins in cancer and chemoresistant tumours that may form the basis for new cancer treatment strategies.

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The Emerging Role of Voltage-Gated Sodium Channels in Tumor Biology

Cited by 45 publications

References 68 publications

SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation

SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance

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