Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging

Our plain-English summary of Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging, by H.T. Le, M. Staelens, D. Lazzari, et al (Cells, 2022).

The study

• Authors: H.T. Le, M. Staelens, D. Lazzari, G. Chan, J.A. Tuszyński
• Journal: Cells
• Published: 2022;11(17)
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1-3 V/cm) alternating EFs with intermediate frequencies (100-500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields' frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle.

In plain English

This was a laboratory study of human cells grown in dishes. It did not involve asbestos or people. The authors exposed two cell lines, HeLa (cervical carcinoma) and MCF-10A (breast epithelial), to tumour-treating fields, which are low-intensity alternating electric fields, for 18 hours and filmed the cells dividing. HeLa cells received fields at 100 or 200 kHz, either alternating between two perpendicular directions or in one direction only. With two-directional 100 kHz fields, median mitosis in HeLa cells was 40 minutes longer than the 50 minutes seen in unexposed cells. Median cytokinesis (the final split into two cells) was 210 minutes versus 110 minutes (p less than 0.001 for both). Fields at 200 kHz had a significantly weaker effect. Using one direction instead of two made no significant difference to mitosis, with only weak evidence of a difference for cytokinesis. In MCF-10A cells, median mitosis was 110 minutes longer and median cytokinesis 40 minutes longer with fields. The authors concluded that two-directional 100 kHz fields had the largest effect on HeLa cells. Cells were not followed beyond 17 hours of imaging.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: in vitro laboratory experiment using live-cell (time-lapse) imaging of cultured cell lines
• Who was studied: HeLa (human cervical carcinoma) and MCF-10A (human breast epithelial) cell lines, obtained at the University of Alberta's Cross Cancer Institute. Mitosis durations were measured for 164, 172, 205 and 195 HeLa cells (control, 100 kHz 1-1, 100 kHz 1-0, 200 kHz 1-1) and for 110 control and 67 exposed MCF-10A cells.
• Exposure: Tumour-treating fields (low-intensity alternating electric fields) for 18 hours at 100 or 200 kHz, with a 1-1 duty cycle (alternating between two perpendicular directions) or a 1-0 duty cycle (one direction). No asbestos exposure was studied.
• Main results:
  • HeLa cells, 100 kHz, 1-1: median mitosis was 50 min in control cells and was 40 min longer in exposed cells (p less than 0.001)
  • HeLa cells, 100 kHz, 1-1: median cytokinesis was 210 min in exposed cells versus 110 min in control cells (p less than 0.001)
  • 80% of control HeLa cells completed the whole division process within 3 hours, compared with 3.5% of HeLa cells exposed to 100 kHz, 1-1 fields
  • HeLa cells: 200 kHz fields had a significantly weaker effect on mitosis and cytokinesis than 100 kHz fields (p less than 0.001)
  • HeLa cells: no significant difference in mitosis duration between one-direction and two-direction fields (p greater than 0.1)
  • HeLa cells: median cytokinesis was 30 min longer with two-direction fields than with one-direction fields, which the authors described as weak evidence (0.01 less than p less than 0.05)
  • MCF-10A cells, 100 kHz, 1-1: median mitosis was 110 min longer than in control cells (p less than 0.001)
  • MCF-10A cells, 100 kHz, 1-1: median cytokinesis was 40 min longer than in control cells (p less than 0.001)
  • Exposed MCF-10A cells did not show the prevalence of multinucleated daughter cells that was seen in exposed HeLa cells
• The authors' conclusion: The authors concluded that 100 kHz fields applied in two perpendicular directions had the largest anti-mitotic effect on HeLa cells, with only a marginal, not strongly significant, gain over one direction at the same frequency.
• Limitations the authors state:
  • Treated cells were not followed after the 17 hours of imaging
  • Some exposed HeLa cells had not finished cytokinesis within the 17-hour imaging period, so fewer exposed cells had a cytokinesis duration measured
  • The MCF-10A control group came from two independent experiments rather than three
  • The finding on one versus two field directions may differ in other cell types

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma.

Related studies

• Tumour treating fields therapy for glioblastoma: current advances and future directions — O. Rominiyi, A. Vanderlinden, et al. (2021)
• Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma — D. Chen, S.B. Le, et al. (2022)
• The Mechanisms of Action of Tumor Treating Fields — J.C. Moser, E. Salvador, et al. (2022)
• A review of tumor treating fields (TTFields): advancements in clinical applications and mechanistic insights — X. Li, K. Liu, et al. (2023)
• The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts — N.A. Oberheim-Bush, W. Shi, et al. (2022)
• Real-time non-invasive detection of inhalable particulates delivered into live mouse airways — M. Donnelley, K.S. Morgan, et al. (2009)

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