Background: Calcium electroporation is a new experimental anti-cancer treatment where calcium is internalized into cells by application of short, high voltage pulses. Calcium electroporation has been shown to induce tumor necrosis associated with ATP depletion while the effect on normal fibroblasts was limited when investigated in a 3D in vitro spheroid model. We aimed to investigate the effect of calcium electroporation in combination with metformin, a drug that affects intracellular ATP level. We also aimed to study the relationship between the viability and intracellular ATP levels after calcium electroporation in vitro.
Methods: In this study, we investigated the effect of calcium electroporation with metformin on NMRI-Foxn1nu mice in vivo on tumor size, survival, and intracellular ATP. We further investigated viability and intracellular ATP level in vitro after calcium electroporation in two human cancer cell lines: Breast (MDA-MB231) and colon (HT29), and in normal human fibroblasts (HDF-n), as well as investigating viability in human bladder cancer cells (SW780) and human small cell lung cancer cells (H69) where we have previously published intracellular ATP levels.
Results: Calcium electroporation significantly reduced the size and ATP level of bladder cancer tumors treated in vivo but no increased effect of metformin combined with calcium electroporation was shown on neither tumor size, survival, nor ATP level. Calcium electroporation in vitro significantly decreased viability compared with calcium alone (p<0.0001 for calcium concentrations from 0.5 mM for H69, HDF-n, and MDA-MB231; p<0.0001 for calcium concentrations from 1 mM for HT29 and SW780). Intracellular ATP levels decreased significantly after calcium electroporation (p<0.05), however no correlation between intracellular ATP level and viability after treatment was observed.
Conclusion: Calcium electroporation caused reduced tumor size, increased survival, and acute ATP depletion in vivo. This effect was not augmented by metformin. Calcium electroporation is a possible novel anti-cancer treatment that has been shown to cause cell death associated with acute ATP depletion in vitro and in vivo.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526525 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181839 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
A Flexible, Implantable, Bioelectronic Electroporation Device for Targeted Ablation of Seizure Foci in the Mouse Brain.
Sensors (Basel)
December 2024
Mines Saint-Etienne, Centre CMP, Département BEL, F-13541 Gardanne, France.
The primary method of treatment for patients suffering from drug-resistant focal-onset epilepsy is resective surgery, which adversely impacts neurocognitive function. Radio frequency (RF) ablation and laser ablation are the methods with the most promise, achieving seizure-free rates similar to resection but with less negative impact on neurocognitive function. However, there remains a number of concerns and open technical questions about these two methods of thermal ablation, with the primary ones: (1) heating; (2) hemorrhage and bleeding; and (3) poor directionality.
View Article and Find Full Text PDFThe additive effect of 17β-estradiol on the modulation of electrochemotherapy with calcium ions or cisplatin in human clear carcinoma cells.
Biomed Pharmacother
December 2024
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw 50-556, Poland.
Calcium electroporation (CaEP) is an efficient approach for ovarian cancer treatment. It causes cell death by introducing elevated levels of calcium into cells. In this work, the research focused on two types of cell lines: CHO-K1, representing normal ovary cells, and OvBH-1, representing ovarian clear carcinoma cells.
View Article and Find Full Text PDFReversible Electroporation for Cancer Therapy.
Br J Radiol
November 2024
Department of Diagnostic and Interventional Radiology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, LS9 7TF.
Reversible electroporation refers to the use of high voltage electrical pulses on tissues to increase cell membrane permeability. It allows targeted delivery of high concentrations of chemotherapeutic agents including cisplatin and bleomycin, a process known as electrochemotherapy (ECT). It can also be used to deliver toxic concentrations of calcium and gene therapies that stimulate an anti-tumour immune response.
View Article and Find Full Text PDFEnhancing lung cancer growth inhibition with calcium ions: Role of mid- and high-frequency electric field pulses.
Biomed Pharmacother
December 2024
Wroclaw Medical University, Faculty of Pharmacy, Department of Molecular and Cellular Biology, Wroclaw, Poland; Medical University Hospital, Wroclaw, Poland. Electronic address:
Calcium electroporation (CaEP) involves the combination of calcium ions with electroporation, which is induced by pulsed electric fields (PEFs). This study explores the application of high-frequency unipolar nanosecond pulsed electric fields (nsPEFs: 8-14 kV/cm, 200 ns, 10 kHz, 100 kHz, 1 MHz repetition frequency pulse bursts, n = 100) and their potential in inhibiting lung cancer cell growth. As a reference, standard microsecond range parametric protocols were used (100 µs x 8 pulses).
View Article and Find Full Text PDFNumerical assessments of geometry, proximity and multi-electrode effects on electroporation in mitochondria and the endoplasmic reticulum to nanosecond electric pulses.
Sci Rep
October 2024
Department of Electrical and Computer Engineering, Texas Tech University, Lubbock, TX, 79409, USA.
Article Synopsis
- - This study examines how complex cellular structures, specifically Jurkat cells with features like the endoplasmic reticulum and mitochondria, respond to external electric pulses by modeling transmembrane potential and electroporation.
- - Simulations reveal that electroporation requires a stronger electric field for the endoplasmic reticulum compared to the inner mitochondrial membrane, which is more susceptible to poration, and may be linked to increased intracellular calcium levels.
- - The research also explores how repeated electric pulses and electrode placement enhance membrane poration, while acknowledging that although more complex models could improve accuracy, basic trends in findings are likely to persist.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!