Low-Frequency Ultrasound Selectively Targets Oral Cancer Cells

Oral cancer, a malignancy of the mouth, is a major health challenge in India where tobacco and areca nut use contribute substantially to the disease burden. Standard surgery, chemotherapy, and radiotherapy can injure healthy tissues, diminishing function and quality of life. Therapeutic options that better spare normal cells are needed to improve outcomes. To help address this challenge, researchers have now tested an ultrasound‑based approach designed to selectively target oral cancer cells.

The team from the Indian Institute of Science (IISc), working with clinicians at MS Ramaiah Medical College and Hospitals, evaluated ultrasound mechanostimulation in patient‑derived oral tumor samples representing variation among Indian patients. The investigators examined whether controlled, low‑frequency mechanical energy from ultrasound could discriminate between malignant and normal oral epithelial cells. Their goal was to identify a noninvasive strategy that exploits tumor‑specific biomechanical weaknesses.

The study found that oral cancer cells were highly vulnerable to the moderate mechanical forces produced by ultrasound, while healthy oral epithelial cells remained unaffected. The observed susceptibility was linked to reduced levels of Tropomyosin 2.1, a mechanosensory protein that enables cells to sense and withstand physiologically relevant mechanical stimulation. These data indicate a mechanistic basis for selective cell death induced by ultrasound in oral cancer.

The researchers also reported functional effects on tumor aggressiveness. Ultrasound exposure markedly reduced cancer cell migration and invasion. Using a three‑dimensional co‑culture platform that mimics the oral tumor microenvironment, the approach disrupted the dense, capsule‑like barrier created by cancer‑associated cells around the tumor core, a structure that typically prevents drugs and immune cells from reaching the core and contributes to treatment failure.

Because ultrasound is noninvasive and already approved for multiple medical applications, the findings point to a potential pathway for safer, more targeted oral cancer treatment pending validation in advanced preclinical models. The authors note that mechanostimulation could also be explored in other accessible cancers, such as breast and skin. The research is published in Materials Today Bio.

“The novelty of this study lies in showing how ultrasound mechanostimulation can selectively target oral cancer cells by exploiting their mechanical weakness,” said Ajay Tijore, assistant professor at the Department of Bioengineering, Indian Institute of Science. "Instead of using heat or drugs, this approach uses moderate mechanical forces to damage cancer cells beyond their ability to recover."

“What surprised us most was the consistency of the response across cancer cells derived from multiple patients from different cancer stages. They were highly vulnerable to ultrasound, while normal cells were much less affected,” said Rashmita Luha, Ph.D. student in the Department of Bioengineering and first author.

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