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Time‐Dependent Effects of Low‐Intensity Pulsed Ultrasound on Apoptosis and Autophagy in Malignant Melanoma Stem Cells

Year: 2025

Type: article

Abstract: ABSTRACT Cancer stem cells (CSCs) in malignant melanoma contribute to therapeutic resistance and tumour recurrence. While low‐intensity pulsed ultrasound (LIPUS) has been proposed as a non‐invasive strategy to induce cell death, its effects on CSC‐specific apoptotic and autophagic responses remain unclear. This study aimed to explore the time‐dependent effects of LIPUS on apoptosis and autophagy in CD133+ melanoma CSCs and CD133− non‐stem melanoma cells. Human melanoma cells (CHL‐1) were sorted via FACS into CD133+ and CD133− populations. Cells were exposed to LIPUS (1 MHz, 20% duty cycle, 1 W/cm2) for 1, 5, and 10 min. Protein expression levels of Caspase‐3, Caspase‐8, mTOR, and LC3 were evaluated via immunofluorescence and quantified by image‐based analysis. Both cell populations showed significant increases in Casp3, Casp8, mTOR, and LC3 intensities following LIPUS application. Notably, CD133+ cells exhibited delayed but sustained increases in Casp3 and LC3 expression, while CD133− cells responded more rapidly. mTOR activity demonstrated distinct temporal dynamics between the two groups, suggesting differential modulation of autophagy‐related pathways. LIPUS triggers temporally distinct apoptotic and autophagic responses in melanoma CSCs and non‐stem cancer cells. These findings suggest a potential therapeutic avenue to selectively disrupt CSC survival mechanisms using mechanical stimulation.

Source: Journal of Cellular and Molecular Medicine

DOI: 10.1111/jcmm.70687

Authors: Omer Dikici, Berrin Ozdil, Taha Kadir Yesin, Aylin Dikici, Yasemin Adalı, Huseyin Aktug