Electrical voltage patterns in healthy cells serve as a guide for a well-organized cell development process. The opposite occurs with cancer, though. Cells lose their specialized roles, start growing into tumors, and spread into other tissues—a process known as metastasis. This process also causes a breakdown in the cell’s normal electrical patterns. Metastasis continues to be the biggest cause of death in cancer patients, and drugs that modulate the electrical patterns of tumor cells may hold promise as novel treatments.
Researchers at Tufts University recently demonstrated that tumor cell invasion in vitro and metastasis in animal models of breast cancer can both be reduced considerably by altering the voltage patterns in tumor cells using ion channel blocking drugs that have already received FDA approval for the treatment of other illnesses.
An accelerated path to approval for the treatment of cancer may result from the revelation that medications, currently approved for other illnesses, can halt or stop spreading. A large selection of ready-to-use medications could be used for cancer therapy because ion channels, which control the bioelectrical properties of cells, are the third-most frequent targets for current pharmaceuticals.
Triple-negative breast cancer (TNBC), which makes up around 15% of all occurrences of breast cancer, was the focus of a recent Tufts University study. TNBC has a higher likelihood of spreading than any other subtype of breast cancer, thus researchers are concentrating their efforts on treating it because it has a dismal five-year prognosis. The Tufts team was able to demonstrate that modulating the membrane voltage properties of breast cancer cells can affect the progression of metastasis. Using a mouse lung model, they showed a decrease of 50% in the number of metastatic sites.
A wide range of ion channel-target drugs already exist, which affect the ability of cells to conduct positively or negatively charged ions across the cellular membrane. These drugs are used to treat anxiety, pain, metabolism, and cardiovascular disorders.
In the study, Tufts scientists genetically over-expressed potassium ion channels in tumor cells, which caused the inside of the cells to become more negatively charged. As a result of the voltage imbalance, tumor growth and metastasis in plated cells and animal models were both accelerated. In contrast, blocking the ion channels resulted in a restoration of normal cell voltages, decreased tumor cell invasion, and a markedly reduced rate of metastasis.
Their findings were published in the eBioMedicine:
Potassium channel-driven bioelectric signalling regulates metastasis in triple-negative breast cancer
The efficiency of four FDA-approved potassium ion channel blockers in eliminating tumor cells was compared in the study. Amiodarone, which had the greatest impact on restoring normal cell voltages, was chosen to be tested for its efficacy in treating breast cancer in mice. The medicine, which is authorized for use in treating cardiac rhythm abnormalities, was found to reduce the tumor’s capacity to spread as cells detached and traveled to different places of the body.
The researchers discovered a number of biochemical pathways involved in cell migration by examining the genes that were activated by the voltage shift. The ion channel-blocking drug’s actions were consistent with restricting the mobility of the cells, preventing them from straying and developing new tumors.
In addition to current standard-of-care therapies like chemotherapy, the Tufts team will continue to investigate the impact of ion channel blockers on cancer in animal models. Since amiodarone and comparable medications have already received human use approval, Phase I clinical trials in small groups of cancer patients may begin soon.
More and more studies are confirming the importance of ion channel modulation in cancer treatment and therapy. Although traditionally used for cardiac and neurological research, dedicated ion channel research devices such as Fluxion’s IonFlux Mercury automated patch clamp systems are perfectly suited for potassium channel modulation for cancer research.
Ali Yehia has a Ph.D. in Cardiac Electrophysiology from McGill University. He has been involved in ion channel screening using Automate Patch Clamp since 2006. He joined Fluxion Biosciences in 2012, where he developed ion channel assays and IonFlux Mercury systems. He was the Chief Scientific Officer at Fluxion before moving to Cell Microsystems as the new Senior Director of the IonFlux product.
In the ongoing battle against antibiotic-resistant bacteria, or “superbugs,” scientists are constantly seeking innovative tools to understand the mechanisms of resistance and develop effective treatments. One such groundbreaking technology is shear flow systems, which have emerged as game-changers in microbiological research. By simulating the dynamic conditions of bacteria’s natural environments, such as the human body or food processing, shear flow systems provide unique insights into bacterial behavior and resistance mechanisms that traditional static methods simply cannot achieve. In this blog post, we’ll explore the benefits of using shear flow systems to combat antibiotic resistance and develop next-generation therapies.
Antibiotic resistance is a complex phenomenon influenced by a variety of factors, including genetic mutations, horizontal gene transfer, and the formation of biofilms. Traditional laboratory methods often fail to capture the dynamic nature of these processes, leading to incomplete or misleading results. Shear flow systems address this limitation by providing a more realistic environment for bacterial growth and interaction. Here’s how:
1. Mimicking Real-World Conditions
In the human body, bacteria are rarely in a static state. They are constantly exposed to fluid flow, such as blood circulation or urine flow, which influences their behavior and resistance mechanisms. Shear flow systems can replicate these conditions, allowing researchers to study how bacteria respond to antibiotics under realistic physiological conditions. This is critical for understanding how resistance develops and persists in vivo. This benefit was recently highlighted in a webinar presented by Dr. Katharina Richter, a microbiology researcher from the University of Adelaide in Australia. Using a high-throughput BioFlux Shear Flow System, Dr. Richter and her team were able to test 3 different methods of superbug treatments under physiological conditions.
2. Studying Biofilm Formation and Resistance
Biofilms—structured communities of bacteria encased in a protective matrix—are a major contributor to antibiotic resistance. Biofilms are notoriously difficult to treat because they shield bacteria from antibiotics and the immune system. Shear flow systems enable researchers to study biofilm formation in real time, observing how bacteria adhere to surfaces, form microcolonies, and develop resistance under flow conditions. For example, using a BioFlux, Dr. Richter was able to leverage high-resolution imaging to obtain unprecedented insight into the biofilm killing and prevention efficacy of a copper and diethyldithiocarbamate (DDC) combination nanoparticles¹. The group is currently investigating the use of a Cu-DDC infused gel that can be injected into wounds that are at high risk for chronic infection, such as hernia.
The study of biofilm communities presents unique challenges in experimental design and analysis. While mixed bacterial populations offer fascinating insights into microbial interactions and community dynamics, accurately characterizing and investigating these complex systems has previously required sophisticated and tedious technical approaches. Here, we will discuss advances in technology that have helped to simplify and streamline polymicrobial investigations.
Throughout the last decade, a trend for growing and assaying biofilms under shear flow has gained traction among microbiologists. The rationale for investigating biofilms under flow is multi-dimensional. A recent Cell Microsystems survey asked why microbiologists are using shear flow found that the top responses were:
Of the scientists surveyed, 40% indicated that they use a BioFlux Shear Flow System. This system provides unique advantages over other methods to induce shear stress, such as slide-based parallel plate flow chambers and benchtop rockers.
BioFlux uses microfluidic channels embedded onto the bottom of standard-sized 6, 24, or 48-well plates to create isolated and independent flow chambers where user-defined wall shear stress is initiated and maintained by digitally controlled air pressure. This not only simplifies the setup and experimental processes but also ensures that experiments are contained and do not contaminate the shear flow system.
Although shear flow has been thoroughly demonstrated to improve the biological relevance of biofilm investigations1, an often overlooked aspect of biofilm physiology is the significant role that multicellular aggregates play in biofilm formation2. When investigating Pseudomonas aeruginosa, it has been demonstrated that multicellular aggregates lead to faster biofilm formation and enhanced resistance to antimicrobials and immune responses3. In addition, multispecies microbial aggregates have been shown to dominate single cells in human saliva4. Together, these data show that aggregates are important areas of investigation because they are more likely to represent physiological biofilm formation and growth.
