Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation

Abstract Purpose Currently, tumor-treating field (TTField) therapy utilizes a single “optimal” frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characte...

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Main Authors: Austin R. Smothers, Jason R. Henderson, John J. O’Connell, Jonathan M. Stenbeck, Delphine Dean, Brian W. Booth
Format: Article
Language:English
Published: BMC 2023-06-01
Series:Cancer Cell International
Subjects:
Online Access:https://doi.org/10.1186/s12935-023-02959-x
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author Austin R. Smothers
Jason R. Henderson
John J. O’Connell
Jonathan M. Stenbeck
Delphine Dean
Brian W. Booth
author_facet Austin R. Smothers
Jason R. Henderson
John J. O’Connell
Jonathan M. Stenbeck
Delphine Dean
Brian W. Booth
author_sort Austin R. Smothers
collection DOAJ
description Abstract Purpose Currently, tumor-treating field (TTField) therapy utilizes a single “optimal” frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields. Methods We developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells. Results We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control. Conclusion TTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.
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spelling doaj.art-5087cb2efb614be39af589b60e32a6722023-06-11T11:25:47ZengBMCCancer Cell International1475-28672023-06-012311810.1186/s12935-023-02959-xOptimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulationAustin R. Smothers0Jason R. Henderson1John J. O’Connell2Jonathan M. Stenbeck3Delphine Dean4Brian W. Booth5Center for Innovative Medical Devices and Sensors (REDDI Lab), Clemson UniversityQuiverent LLCPrisma Health Cancer Institute, Prisma HealthPrisma Health Cancer Institute, Prisma HealthCenter for Innovative Medical Devices and Sensors (REDDI Lab), Clemson UniversityDepartment of Bioengineering, Clemson UniversityAbstract Purpose Currently, tumor-treating field (TTField) therapy utilizes a single “optimal” frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields. Methods We developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells. Results We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control. Conclusion TTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.https://doi.org/10.1186/s12935-023-02959-xBreast cancerElectric field intensityFrequency modulationOscillating electric fieldsRadiotherapyTriple-negative breast cancer (TNBC)
spellingShingle Austin R. Smothers
Jason R. Henderson
John J. O’Connell
Jonathan M. Stenbeck
Delphine Dean
Brian W. Booth
Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation
Cancer Cell International
Breast cancer
Electric field intensity
Frequency modulation
Oscillating electric fields
Radiotherapy
Triple-negative breast cancer (TNBC)
title Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation
title_full Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation
title_fullStr Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation
title_full_unstemmed Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation
title_short Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation
title_sort optimization of tumor treating field therapy for triple negative breast cancer cells in vitro via frequency modulation
topic Breast cancer
Electric field intensity
Frequency modulation
Oscillating electric fields
Radiotherapy
Triple-negative breast cancer (TNBC)
url https://doi.org/10.1186/s12935-023-02959-x
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