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Updated: May 23, 2025

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Ultrasound-mediated mechanical forces activate selective tumor cell apoptosis.

Ajay Tijore1,2, Felix Margadant1,3, Nehal Dwivedi3

  • 1Mechanobiology Institute National University of Singapore Singapore.

Bioengineering & Translational Medicine
|March 10, 2025
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Summary

Ultrasound mechanical forces induce tumor cell apoptosis via Piezo1 channels, sparing normal cells. This non-invasive approach shows promise for augmenting cancer treatments.

Keywords:
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Area of Science:

  • Biophysics
  • Cell Biology
  • Oncology

Background:

  • Mechanical stretching induces tumor cell apoptosis and promotes normal cell growth.
  • Ultrasound generates nanoscale mechanical stresses similar to those from mechanical stretching.

Purpose of the Study:

  • To investigate the effect of ultrasound-mediated mechanical forces on tumor and normal cell survival.
  • To elucidate the molecular mechanisms underlying ultrasound-induced tumor cell death.

Main Methods:

  • Application of ultrasound to various tumor cell lines and normal cells.
  • Analysis of apoptosis pathways, including mitochondrial pathways and calcium signaling.
  • In vivo studies using mouse models (CT26 tumors) and chick chorioallantoic membrane (CAM) models.
  • Testing on patient-derived pancreatic tumor organoids.

Main Results:

  • Ultrasound induces apoptosis in tumor cells through a calpain-dependent mitochondrial pathway.
  • This process relies on calcium entry via mechanosensitive Piezo1 channels.
  • Tumor cell apoptosis is observed across diverse cell lines and tissues of origin, while normal cells remain unaffected.
  • In vivo studies demonstrated ultrasound-mediated tumor cell killing in mouse and CAM models with minimal damage to surrounding tissues.
  • Patient-derived pancreatic tumor organoids were also effectively killed by ultrasound treatment.

Conclusions:

  • Ultrasound-mediated mechanical forces provide a general mechanism for inducing tumor cell apoptosis.
  • The Piezo1 channel and calcium signaling are critical for this effect.
  • Ultrasound represents a potential safe and non-invasive therapeutic strategy for cancer treatment augmentation.