Piezo1-mediated cellular apoptosis in breast cancer cells triggered by ultrasound and microbubbles
Nina Qu1, Menglu Bi2, Qingkai Meng3
1Department of Ultrasound Medicine, Yantai Yuhuangding Hospital, Yantai 264000, Shandong, China. ninebaby1006@126.com.
Abstract:
Piezo1 ion channels play a crucial role in apoptosis regulation in human breast cancer cells (MCF-7), and this study evaluates the effects of Piezo1 agonist (Yoda1), inhibitor (GsMTx4), and ultrasound microbubble (USMB) treatment on cellular apoptosis pathways. In this research, in vitro cultures of normal breast epithelial cells (MCF-10A) and cancer cell lines (MCF-7, MDA-MB-231) were analyzed by Western blotting to determine Piezo1 protein levels, with MCF-7 selected for further analysis. Groups included control (untreated), Yoda1, USMB, GsMTx4, and USMB+GsMTx4, and apoptosis rates were measured via flow cytometry. Levels of apoptosis-related proteins (Bcl-2, Bax), endoplasmic reticulum stress proteins (GRP-78, Caspase 12), and mitochondrial pathway proteins (Cyt-c, Caspase 3, Caspase 9) were quantified, while JC-1 and Ca2+ fluorescent probes were used to assess mitochondrial membrane potential and intracellular Ca2+ concentration. Results showed MCF-7 cells expressed the highest Piezo1 levels. Yoda1 and USMB both markedly increased apoptosis, enhanced ER stress, and induced the mitochondrial apoptosis pathway in comparison to control, while GsMTx4 had the opposite effect and USMB reversed GsMTx4's phenotype. The USMB group exhibited the lowest mitochondrial membrane potential and the highest Ca2+ fluorescence intensity. These findings indicate that USMB activates ER stress via Piezo1, induces mitochondrial dysfunction, elevates intracellular Ca2+, and thereby promotes apoptosis in breast cancer cells..
Insights
Ultrasound microbubble (USMB) treatment and Piezo1 agonist (Yoda1) promote breast cancer cell apoptosis by activating ER stress and mitochondrial pathways. The Piezo1 inhibitor (GsMTx4) reversed these effects, highlighting Piezo1
Area of Science:
- Cell Biology
- Oncology
- Biophysics
Background:
- Piezo1 ion channels are mechanosensitive channels implicated in cellular processes.
- Dysregulation of apoptosis contributes to breast cancer progression.
- Targeting Piezo1 presents a potential therapeutic strategy for breast cancer.
Purpose of the Study:
- To investigate the role of Piezo1 in apoptosis of human breast cancer cells (MCF-7).
- To evaluate the effects of Piezo1 modulation using Yoda1 (agonist) and GsMTx4 (inhibitor) on apoptosis.
- To assess the impact of ultrasound microbubble (USMB) treatment on Piezo1-mediated apoptosis.
Main Methods:
- Western blotting to quantify Piezo1 protein expression in breast cancer cell lines.
- Flow cytometry to measure apoptosis rates.
- Assessment of apoptosis-related proteins, ER stress markers, and mitochondrial pathway proteins.
- Mitochondrial membrane potential and intracellular calcium ion (Ca2+) concentration measurements using fluorescent probes.
Main Results:
- MCF-7 cells exhibited the highest Piezo1 expression.
- Yoda1 and USMB significantly increased apoptosis, ER stress, and mitochondrial pathway activation.
- GsMTx4 inhibited apoptosis and reversed USMB-induced effects.
- USMB treatment led to decreased mitochondrial membrane potential and increased intracellular Ca2+.
Conclusions:
- USMB treatment activates ER stress through Piezo1 in breast cancer cells.
- USMB induces mitochondrial dysfunction and elevates intracellular Ca2+, promoting apoptosis.
- Modulating Piezo1 activity offers a potential therapeutic avenue for breast cancer treatment.
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