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Updated: Aug 9, 2025

Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures
Published on: July 27, 2022
Electric Fields Regulate In Vitro Surface Phosphatidylserine Exposure of Cancer Cells via a Calcium-Dependent Pathway
Ahmet Kaynak1,2, Kombo F N'Guessan2,3, Priyankaben H Patel4
1Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA.
Abstract:
Cancer is the second leading cause of death worldwide after heart disease. The current treatment options to fight cancer are limited, and there is a critical need for better treatment strategies. During the last several decades, several electric field (EF)-based approaches for anti-cancer therapies have been introduced, such as electroporation and tumor-treating fields; still, they are far from optimal due to their invasive nature, limited efficacy and significant side effects. In this study, we developed a non-contact EF stimulation system to investigate the in vitro effects of a novel EF modality on cancer biomarkers in normal (human astrocytes, human pancreatic ductal epithelial -HDPE-cells) and cancer cell lines (glioblastoma U87-GBM, human pancreatic cancer cfPac-1, and MiaPaCa-2). Our results demonstrate that this EF modality can successfully modulate an important cancer cell biomarker-cell surface phosphatidylserine (PS). Our results further suggest that moderate, but not low, amplitude EF induces p38 mitogen-activated protein kinase (MAPK), actin polymerization, and cell cycle arrest in cancer cell lines. Based on our results, we propose a mechanism for EF-mediated PS exposure in cancer cells, where the magnitude of induced EF on the cell surface can differentially regulate intracellular calcium (Ca2+) levels, thereby modulating surface PS exposure.
Insights
This study introduces a novel non-contact electric field (EF) system to modulate cancer biomarkers. Moderate EF exposure effectively altered cell surface phosphatidylserine (PS) and induced cancer cell cycle arrest.
Area of Science:
- Biophysics
- Oncology
- Cell Biology
Background:
- Cancer is a leading cause of death with limited treatment options.
- Existing electric field (EF) therapies have drawbacks like invasiveness and side effects.
- There is a need for improved, non-invasive anti-cancer strategies.
Purpose of the Study:
- To develop and evaluate a non-contact EF stimulation system.
- To investigate the in vitro effects of a novel EF modality on cancer biomarkers.
- To explore the underlying mechanisms of EF-mediated cancer cell modulation.
Main Methods:
- Developed a non-contact EF stimulation system.
- Applied EF stimulation to normal and cancer cell lines (glioblastoma, pancreatic cancer).
- Analyzed modulation of cancer biomarkers, including cell surface phosphatidylserine (PS), p38 MAPK, actin polymerization, and cell cycle progression.
Main Results:
- The novel EF modality successfully modulated cell surface phosphatidylserine (PS) in cancer cells.
- Moderate amplitude EF, but not low amplitude EF, induced p38 mitogen-activated protein kinase (MAPK) activation.
- Moderate EF exposure led to actin polymerization and cell cycle arrest in cancer cell lines.
Conclusions:
- The non-contact EF system shows potential for anti-cancer therapy by modulating key cancer biomarkers.
- EF-induced changes in intracellular calcium (Ca2+) levels are proposed as a mechanism for PS exposure.
- This EF modality offers a promising avenue for developing less invasive and more effective cancer treatments.
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