Related Experiment Video

Updated: Jul 26, 2025

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
06:19

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches

Published on: June 16, 2023

3.2K

Voltage-Gated Sodium Channel NaV1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells

Piyasuda Pukkanasut1, Jason Whitt2, Rachael Guenter2

  • 1Department of Chemistry, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Cancers
|June 22, 2023
PubMed

Insights

Voltage-gated sodium channel (VGSC) NaV1.7 is expressed in aggressive medullary thyroid cancer (MTC). A novel inhibitor, SV188, effectively blocks NaV1.7, reducing MTC cell viability and invasion.

Area of Science:

  • Oncology
  • Neuroscience
  • Pharmacology

Background:

  • Medullary thyroid cancer (MTC) is a neuroendocrine tumor with limited targeted therapies.
  • Voltage-gated sodium channels (VGSCs) are implicated in cancer progression, but their specific roles in MTC are unclear.

Purpose of the Study:

  • To investigate the expression of VGSC subtype NaV1.7 in MTC.
  • To evaluate the therapeutic potential of a novel NaV1.7 inhibitor, SV188, in MTC.

Main Methods:

  • Quantitative RT-PCR, Western blotting, and immunohistochemistry were used to assess NaV1.7 expression in MTC cell lines and patient specimens.
  • Whole-cell patch-clamp electrophysiology was employed to study the inhibitory effects of SV188 on NaV1.7 currents.
  • Cell viability, invasion, and migration assays were performed to evaluate SV188's anti-cancer effects on MTC cells.

Main Results:

  • NaV1.7 was uniquely expressed in aggressive MTC tissues and cell lines, but not in normal thyroid cells.
  • SV188 inhibited NaV1.7 currents with an IC50 of 3.6 µM via a voltage- and use-dependent mechanism.
  • SV188 reduced MTC cell viability (IC50 ~8.5-9.3 µM) and significantly inhibited invasion and migration of MTC cells with high NaV1.7 expression.

Conclusions:

  • NaV1.7 is a potential therapeutic target in aggressive MTC.
  • SV188 demonstrates promising anti-cancer activity against MTC by inhibiting NaV1.7, suggesting its potential as a novel MTC therapeutic agent.
Keywords:
NaV1.7cell invasioncell viabilitymedullary thyroid cancermetastasisneuroendocrine tumorvoltage-gated sodium channels

More Related Videos

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice00:07

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.4K
Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma06:08

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma

Published on: June 2, 2023

1.8K

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
208
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
8.3K
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
1.5K
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.1K
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
217
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein01:20

Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein

Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
351