Inhibition of Mitochondrial Voltage-Dependent Anion Channels Increases Radiosensitivity of K562 Leukemic Cells

Saenko, Yury; Mastilenko, A.V.; Глущенко, Е. С.; Антонова, А. В.; Свеколкин, В. П.

doi:10.1007/s10517-016-3356-8

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…We observed an increase in cell cycle arrest, which is illustrated as an increase in G2/G1 ratio over time in the irradiated cells pre-treated with DIDS (Fig 1C). We have demonstrated that DIDS has the radiosensitizing effect on K562 cells and is in concordance with previous research [29,30]. Recently a large number of radiosensitizers that modulate survival pathways have become available, for example inhibitors of histone deacetylase [31], ataxia telangiectasia mutated protein [32], Raf [33], Hsp90 [34], or PI3K/mTOR [35].…”

Section: The Effect Of Dids On Cell Survival and Cell Cycle Progression In Irradiated Cancer Cellssupporting

confidence: 91%

“…DIDS-induced apoptosis in irradiated cells was associated with increased ROS production. It has been shown previously that VDAC inhibition with DIDS leads to loss of mitochondrial membrane potential in irradiated compared to only DIDS treated cells suggesting its VDAC targeting capacity [29]. Additionally, in our earlier report we have shown that increase in ROS production at later time point following IR depends on the mitochondrial complex I activity [3,4].…”

Section: The Effect Of Dids On Ros and No Production In Irradiated Cellsmentioning

confidence: 50%

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The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

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Saenko

et al. 2017

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Section: The Effect Of Dids On Cell Survival and Cell Cycle Progression In Irradiated Cancer Cellssupporting

confidence: 91%

Section: The Effect Of Dids On Ros and No Production In Irradiated Cellsmentioning

confidence: 50%

The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

Skonieczna

Cieślar-Pobuda

Saenko

et al. 2017

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“…The inhibition of VDAC with 500 µM 2′-disulfonic acid (DIDS) induced apoptosis to enhance the effectiveness of radiotherapy. A similar radiosensitization effect was observed for mitochondrial VDACs in human myelogenous leukemia cells [ 63 ].…”

Section: Therapeutic Modalitiessupporting

confidence: 72%

Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms

Djamgoz

2022

Cancers

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Cancer is a global health problem that 1 in 2–3 people can expect to experience during their lifetime. Several different modalities exist for cancer management, but all of these suffer from significant shortcomings in both diagnosis and therapy. Apart from developing completely new therapies, a viable way forward is to improve the efficacy of the existing modalities. One way is to combine these with each other or with other complementary approaches. An emerging latter approach is derived from ionic mechanisms, mainly ion channels and exchangers. We evaluate the evidence for this systematically for the main treatment methods: surgery, chemotherapy, radiotherapy and targeted therapies (including monoclonal antibodies, steroid hormones, tyrosine kinase inhibitors and immunotherapy). In surgery, the possible systemic use of local anesthetics to suppress subsequent relapse is still being discussed. For all the other methods, there is significant positive evidence for several cancers and a range of modulators of ionic mechanisms. This applies also to some of the undesirable side effects of the treatments. In chemotherapy, for example, there is evidence for co-treatment with modulators of the potassium channel (Kv11.1), pH regulation (sodium–hydrogen exchanger) and Na+-K+-ATPase (digoxin). Voltage-gated sodium channels, shown previously to promote metastasis, appear to be particularly useful for co-targeting with inhibitors of tyrosine kinases, especially epidermal growth factor. It is concluded that combining current orthodox treatment modalities with modulators of ionic mechanisms can produce beneficial effects including (i) making the treatment more effective, e.g., by lowering doses; (ii) avoiding the onset of resistance to therapy; (iii) reducing undesirable side effects. However, in many cases, prospective clinical trials are needed to put the findings firmly into clinical context.

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“…dNA repair, cancer stemness, apoptosis (10), cell cycle arrest (11), autophagy (12), and hypoxia (13) have been proposed as essential biological mechanisms leading to radioresistance of cancer cells. Among the radiosensitizers under active investigation or in use are agents targeting hypoxic cells, inhibitors of ion channels (14), regulators of proteins (such as enzymes) (15)(16)(17) or pathways (18) and inhibitors of autophagy (19). However, several limitations exist with these compounds, such as lack of specificity, unclear underlying molecular mechanisms, and adverse effects (3).…”

Section: Introductionmentioning

confidence: 99%

LINCS gene expression signature analysis revealed bosutinib as a radiosensitizer of breast cancer cells by targeting eIF4G1

Xie

Zhou

et al. 2021

Int J Mol Med

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Radioresistance is the predominant cause for radiotherapy failure and disease progression, resulting in increased breast cancer-associated mortality. Using gene expression signature analysis of the Library of Integrated Network-Based cellular Signatures (LINcS) and Gene Expression Omnibus (GEO), the aim of the present study was to systematically identify potential candidate radiosensitizers from known drugs. The similarity of integrated gene expression signatures between irradiated eukaryotic translation initiation factor 4 γ 1 (eIF4G1)-silenced breast cancer cells and known drugs was measured using enrichment scores (ES). drugs with positive ES were selected as potential radiosensitizers. The radiosensitizing effects of the candidate drugs were analyzed in breast cancer cell lines (McF-7, MX-1 and MdA-MB-231) using ccK-8 and colony formation assays following exposure to ionizing radiation. Cell apoptosis was measured using flow cytometry. The expression levels of eIF4G1 and dNA damage response (ddR) proteins were analyzed by western blotting. Bosutinib was identified as a promising radiosensitizer, as its administration markedly reduced the dosage required both for the drug and for ionizing radiation, which may be associated with fewer treatment-associated adverse reactions. Moreover, combined treatment of ionizing radiation and bosutinib significantly increased cell killing in all three cell lines, compared with ionizing radiation or bosutinib alone. Among the three cell lines, MX-1 cells were identified as the most sensitive to both ionizing radiation and bosutinib. Bosutinib markedly downregulated the expression of eIF4G1 in a dose-dependent manner and also reduced the expression of ddR proteins (including ATM, XRcc4, ATRIP, and GAdd45A). Moreover, eIF4G1 was identified as a key target of bosutinib that may regulate dNA damage induced by ionizing radiation. Thus, bosutinib may serve as a potential candidate radiosensitizer for breast cancer therapy.

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Inhibition of Mitochondrial Voltage-Dependent Anion Channels Increases Radiosensitivity of K562 Leukemic Cells

Cited by 6 publications

References 13 publications

The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms

LINCS gene expression signature analysis revealed bosutinib as a radiosensitizer of breast cancer cells by targeting eIF4G1

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