Inhibition of Human Breast Cancer Cell Proliferation by Low‐Intensity Ultrasound Stimulation

Abstract

Objectives-Cancer is characterized by uncontrolled cell proliferation, which makes novel therapies highly desired. In this study, the effects of near-field lowintensity pulsed ultrasound (LIPUS) stimulation on T47D human breast cancer cell and healthy immortalized MCF-12A breast epithelial cell proliferation were investigated in monolayer cultures. Methods-A customized ultrasound (US) exposure setup was used for the variation of key US parameters: intensity, excitation duration, and duty cycle. Cell proliferation was quantified by 5-bromo-2 0-deoxyuridine and alamarBlue assays after LIPUS excitation. Results-At a 20% duty cycle and 10-minute excitation period, we varied LIPUS intensity from to 100 mW/cm 2 (spatial-average temporal-average) to find a gradual decrease in T47D cell proliferation, the decrease being strongest at 100 mW/cm 2. In contrast, healthy MCF-12A breast cells showed an increase in proliferation when exposed to the same conditions. Above a 60% duty cycle, T47D cell proliferation decreased drastically. Effects of continuous wave US stimulation were further explored by varying the intensity and excitation period. Conclusions-These experiments concluded that, irrespective of the waveform (pulsed or continuous), LIPUS stimulation could inhibit the proliferation of T47D breast cancer cells, whereas the same behavior was not observed in healthy cells. The study demonstrates the beneficial bioeffects of LIPUS on breast cancer cells and offers the possibility of developing novel US-mediated cancer therapy.

Low‐intensity pulsed ultrasound prevents prolonged hypoxia‐induced cardiac fibrosis through HIF‐1α/DNMT3a pathway via a TRAAK‐dependent manner

“…LIPUS was reported to improve proliferation of human bone mesenchymal stem cells or endothelial cells 12,13 . However, in some studies, LIPUS was found to suppress the proliferation of visceral preadipocytes or cancer cells 14,15 . Therefore, LIPUS may exert different effects on the proliferation of different cells.…”

Mechanotransduction in tumor dynamics modeling

“…We investigate the potential of 1MHz ultrasound as a selective modification tool for cancer cells with viscosities of 5Pa • s. Our simulations (Figure 8) reveal that ultrasound does not directly affect the proliferation and production of healthy cells. Stress experienced by healthy cells is considerably lower than that experienced by tumor cells, suggesting that ultrasound selectively attacks cancer cells, as reported in [Mittelstein et al, 2020, Katiyar et al, 2020, Lin et al, 2022. We analyze the interplay of tumor and healthy cell growth, influenced by predator-prey dynamics.…”

“…Recent studies have provided compelling evidence of the therapeutic effectiveness of low-intensity ultrasound. Low-intensity ultrasound (LIUS) and its pulsed version (LIPUS), have been proposed to impact cancer cells by two main mechanisms: i) selectively resonating the right diameter cells under the name of oncotripsy, which lies on destroying the cytoskeleton via cavitation [Mittelstein et al, 2020, Heyden and Ortiz, 2016, Lin et al, 2022, Lucchetti et al, 2020, Prentice et al, 2005, and ii) triggered response produced via mechanotransduction signaling pathways [Lin et al, 2022, Lucchetti et al, 2020, Katiyar et al, 2020, Carina et al, 2018, González et al, 2023, Singh et al, 2021, Tijore et al, 2020, Na et al, 2008, Geiger et al, 2009, Vogel, 2006, Broders-Bondon et al, 2018.…”

Synergistic enhancement of cell death by triple combination therapy of docetaxel, ultrasound and microbubbles, and radiotherapy on PC3 a prostate cancer cell line

“…Docetaxel, in addition to cytotoxicity and initiation of apoptosis through microtubule stabilization and impairing mitosis, can alter several genes involved in cell survival and oncogenesis [ 49 , 50 ], which may be associated with the molecular mechanisms by which the triple combination therapy affects the prostate cancer cells. Therapeutic ultrasound with microbubbles can induce a range of cellular bioeffects such as reversible and irreversible sonoporation, endocytosis, exocytosis, calcium influx, apoptosis, autophagy, necrosis, microtubule disruption [ 12 , 15 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. The effect of ionizing radiation on cellular DNA is well known through direct and indirect mechanisms, and nanotechnology has been utilized in enhancing radiotherapy [ 2 , 3 , 58 , 59 ].…”