Study of cellular response induced by low intensity ultrasound frequency sweep pattern on myelomonocytic lymphoma U937 cells

Abstract

Purpose This study will analyze the mechanical effects (immediate lysis) and biological effects (cell survival, apoptosis, cell cycle) on U937 cells subjected to different sonication conditions with increasing and decreasing frequencies and burst rate (number of burst of a repeating signal in a specific time unit), in order to determine the best conditions of sonication to produce high mortality, apoptosis and inhibition of hyperproliferation. Method Cells are been stressed by pulse wave ultrasounds with increasing and decreasing frequencies between 400 and 620 kHz, at burst rates of 0.5, 10, 50 Hz and 50 % duty cycle (percentage of one period in which a signal is active), ultrasound intensities (spatial average-temporal peak) 0.045 and 0.09 W/cm 2 . The sonication durations were 90 and 180 s. Results The decreasing mode was found to be better than the increasing mode for 10 and 50 Hz burst rates, while at 0.5 Hz the increasing mode gave better results for the time of 180 s. For 10 Hz burst rate, decreasing frequency, 180 s, 0.09 W/cm 2 , 20 % survival rate was found; after 6-h incubation, cells showed 13 % of early apoptosis and 11 % of late apoptosis. For these conditions of sonication, the hyperproliferation of cells was inhibited. Conclusion Survival rate decreases for increasing intensity and duration with each burst rate. The best performance is decreasing mode in a range between 620 and 400 kHz, duty cycle 50 %, burst rate 10 Hz. In these conditions after 180 s duration, the average survival rate is 20 %, the survived cells manifest apoptosis after 6-h incubation and hyperproliferation is prevented. The results seem to lead toward a non-invasive and effective purging of leukemic cells.Keywords Low intensity ultrasound Á Cell lysis Á Hyperproliferation apoptosis Á Cell cycle Sommario Scopo Questo studio analizzerà gli effetti meccanici (lisi valutata immediatamente dopo la sonicazione) e gli effetti biologici (sopravvivenza delle cellule, apoptosis e lisi cellulare) su cellule U937 soggette a differenti condizioni di sonicazione con frequenze crescenti e decrescenti, a burst rate (numero di impulsi di un segnale che si ripete in una specifica unità di tempo) variabili, al fine di determinare le migliori condizioni di sonicazione per produrre alta mortalità, apoptosi e inibizione dell'iperproliferazione cellulare. Metodi Le cellule sono state sollecitate con ultrasuoni ad onda pulsata con frequenze crescenti e decrescenti fra 400 e 620 kHz a burst rate di 0.5 Hz, 10 Hz, 50 Hz, con un ciclo di lavoro (frazione di tempo in cui il segnale è attivo in proporzione al tempo totale) del 50 %, intensità (picco spaziale medio-temporale) 0.045 W/cm 2 and 0.09 W/cm 2 . I tempi di sonicazione erano di 90 s e 180 s. Risultati La modalità a frequenza decrescente risultava essere migliore di quella crescente per burst rate 10 Hz e 50 Hz, mentre a 0.5 Hz la modalità a frequenza crescente risultava migliore per un tempo di 180 s. Con un burst rate di 10 Hz, a frequenza decrescente fra 620 e 400 kHz, esposizione per ...

Experimental Data-Mining Analyses Reveal New Roles of Low-Intensity Ultrasound in Differentiating Cell Death Regulatome in Cancer and Non-cancer Cells via Potential Modulation of Chromatin Long-Range Interactions

“…In addition, metabolic disease-risk factors such as hyperlipidemia (37–39), hyperhomocysteinemia (40) and chronic kidney disease (41) accelerate vascular diseases by inducing inflammatory cell death (pyroptosis) or pyrop-apoptosis (37, 40). Interestingly, LIUS was reported to induce apoptosis, autophagy or necrosis in cancer cells including nasopharyngeal cancer cells (42), laryngeal cancer cells (43), hepatocellular cancer cells (43, 44), leukemia cells (45), lymphoma cells (46), and osteosarcoma cells (47). In contrast, LIUS affects various non-cancer immune cells and other cells by regulation of inflammation.…”

Low-frequency ultrasound-induced VEGF suppression and synergy with dendritic cell-mediated anti-tumor immunity in murine prostate cancer cells in vitro

“…For example, Wang 24 reported that the chemotherapeutic effect was enhanced in PCa cells when the low-frequency ultrasonic density was fixed at 113 mw/cm 2 , which likely occurred via alterations in membrane integrity and permeability. Furthermore, it has been reported that the survival rate of tumor cells decreases with increasing ultrasound intensity and duration 25 . As the MB density in tissue is typically low, exogenous MBs, such as SonoVue, are required to increase cavitation in the tumor microenvironment; nonetheless, sonoporation stagnates when MBs reach a certain concentration.…”

Mechanisms of Cellular Effects Directly Induced by Magnetic Nanoparticles under Magnetic Fields

“…The theoretical results also showed that oscillating MNPs may generate ultrasound. Ultrasound is proved to give rise to cell apoptosis or dissolution [86,87]. Cheng et al used rod-shaped MNPs to induce HeLa cell viability decrease by about 2-fold than spherical MNPs with the temperature rise of 1.7 ∘ C after being exposed to an AMF (35 kHz), suggesting that AMF-induced oscillation of MNPs was able to mechanically damage cancer cells in vitro [40].…”