Effects of dissolved gases and an echo contrast agent on apoptosis induced by ultrasound and its mechanism via the mitochondria-caspase pathway

Honda, Hidemi; Zhao, Qing‐Li; Kondo, Takashi

doi:10.1016/s0301-5629(02)00509-4

Cited by 110 publications

(79 citation statements)

References 37 publications

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“…Since the first discovery of ultrasound being capable of inducing apoptosis [5,[9][10][11][12][13][14][15][16][17][18][19], the exact mechanisms of apoptosis caused by ultrasound are unknown and only a few documentations can be found challenging this issue. The involvement of Ca 2+ , free radicals [15], cell membrane damage [12,13] and DNA damage with p53 activation [10] have been proposed for the mechanisms of apoptosis induced by ultrasound.…”

Section: Resultsmentioning

confidence: 99%

“…Many nonapoptotic cells, however, are generated by ultrasound-induced apoptosis [11,[13][14][15] and more extensive research on ultrasound-induced cell death is required. Parameters where apoptosis dominates cell death should be determined both in vitro and in vivo in order to make this technique applicable for clinical use.…”

Section: Resultsmentioning

confidence: 99%

“…It has also become evident that ultrasound can cause cell death by an apoptotic mechanism as well as cell lysis or necrotic cell death both in vitro [9][10][11][12][13][14][15][16][17][18] and in vivo [5,19]. The triggers and the molecular pathway to lead each cell death mechanism are not well elucidated, and should be clarified for overall understanding of the ultrasound-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

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Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2

Kinoshita¹,

Eguchi²,

Hynynen³

2007

Biochemical and Biophysical Research Communications

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The molecular mechanisms underlying ultrasound-induced apoptosis remain poorly understood. We have demonstrated that in Jurkat cells, the over-expression of the anti-apoptotic protein Bcl-2 inhibited ultrasound-induced apoptosis, but not necrosis. Inhibition of caspase activity also protected the cells from apoptosis, but not from necrosis, showing the involvement of different mechanisms in ultrasound-induced apoptosis and necrosis. Bak, a pro-apoptotic member of the Bcl-2 family proteins, was activated by ultrasound and its activation was completely inhibited by Bcl-2 overexpression, but not by caspase inhibition. Antioxidant N-acetyl cysteine did not protect the cells from ultrasound-induced apoptosis or necrosis, nor did the inhibition of either c-Jun N-terminal kinase or p38, key factors in the radical oxygen species (ROS)-mediated cell stress response, suggesting that ROS do not play a crucial role in ultrasound-induced apoptosis. Our results confirm that ultrasound induces apoptosis via a pathway that involves Bak, Bcl-2, and caspases, but not ROS.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2

Kinoshita¹,

Eguchi²,

Hynynen³

2007

Biochemical and Biophysical Research Communications

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“…Various reports have suggested SDT could induce cell death (Honda et al 2002;Firestein et al 2003). The exact mechanisms leading to the cell death, however, are still under investigations.…”

Section: Discussionmentioning

confidence: 99%

ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937 cells

Su¹,

Wang²,

Zhang³

et al. 2014

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Abstract. This study was to investigate the cell killing effect of chlorin-e6 (Ce6)-mediated sonodynamic therapy (SDT) on human leukemia U937 cells and explore the role of ERK signal pathway in the process. The ultrastructure changes of U937 cells induced by ultrasonic irradiation were evaluated by scanning electron microscope (SEM) and transmission electron microscope (TEM). The viability of cells was evaluated by ViaCount assay. Apoptosis was analyzed using flow cytometer as well as fluorescence microscopy with 4'-6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to analyze the expression of mitogen-activated protein kinase (MAPK). Intracellular reactive oxygen species (ROS) and mitochondria membrane potential (MMP) levels were also analyzed by flow cytometer after exposure. Our experiments showed that several distinct sonochemical effects were found after Ce6-mediated SDT treatment. Western blotting analysis indicated that the MAPK was activated. Especially, pre-treatment with ERK inhibitor U0126 could additionally enhance SDT-induced cell viability loss, early-and late-apoptotic rate, chromatin condensation, DNA fragmentation and caspase-3 activation. Besides, a mass of ROS accumulation and a conspicuous loss of mitochondrial membrane potential were detected in U937 cells. These findings suggested ERK signal pathway may deliver a survival signal which counteracts SDT-induced cell death, while combination with U0126 could significantly potentiate the SDT-induced cytotoxic effect in U937 cells.

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“…In 1987, Fecheimer et al were the first to report the biological effects of US cavitation [3], where US was used to deliver cell impermeable fluorescent dextran molecules into mammalian cells by increasing membrane permeability, involving the mechanical production of transient membrane pores. In 1999, Ashush et al were the first to report that US can induce apoptotic cell death in human leukemia cell lines [4], which is also demonstrated in our own research on the activation of the mitochondrial caspase pathway in US-treated leukemia cells [5]. Currently, accumulating evidence indicates that the non-thermal effects of US-induced reactive oxygen species, membrane fluidity, and DNA damage are responsible for cell death.…”

Section: Introductionmentioning

confidence: 94%

DNA Damage Induced by Ultrasound and Cellular Responses

Furusawa¹,

Kondo²

2017

Mol Biol

Self Cite

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Ultrasonic technologies pervade the medical field as a long established imaging modality in clinical diagnostics and, with the emergence of targeted high-intensity focused ultrasound, as a means of thermally ablating tumors. Ultrasound (US) causes multiple thermal and non-thermal effects, such as mechanical and chemical stresses, that can result in damage to the cellular membrane and nucleus, leading to transient membrane pores, alterations in gene expression, and cell death, including apoptosis. On the basis of its biological effects US has been proposed as a new drug delivery and molecular targeting tool for cancer therapy. However, the molecular mechanisms involved in USinduced cell killing are not yet fully understood. Recently, we have reported that the mechanical effects of US elicit DNA single strand as well as double strand breaking-the most cytotoxic form of DNA damage, which initiates subsequent DNA damage response associated with DNA repair, cell cycle arrest, and cell death. Here in the present study we have focused on one of the most significant biological effects of US, i.e., DNA damage and discussed the underlying mechanisms and a unique cellular response. In addition, we have described the characteristic DNA damage response induced by heat stress, which could have caused by the thermal effects of US. Moreover, the study will enrich the literature relevant to furthering our understanding of US for future applications in cancer therapy.

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Effects of dissolved gases and an echo contrast agent on apoptosis induced by ultrasound and its mechanism via the mitochondria-caspase pathway

Cited by 110 publications

References 37 publications

Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2

Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2

ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937 cells

DNA Damage Induced by Ultrasound and Cellular Responses

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