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.

Biomedicines
|February 25, 2023
PubMed

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.

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.3K
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.4K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K