Radiation-Induced Rescue Effect: Insights from Microbeam Experiments

Yu, K.N.

doi:10.3390/biology11111548

Cited by 2 publications

(4 citation statements)

References 95 publications

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“…Therefore, prostaglandins released from irradiated cells to neighboring bystander cells may induce the upregulation of COX-2 expression in cell populations, increasing radioresistance. RIBE-induced radio-adaptive response and rescue effect can be considered as the cellular response to radioresistance [27,28]. Based on the aforementioned reports, we hypothesized that the COX-2 expression and PGE2 production resulting from the RIBE affect the radiosensitivity of bystander cancer cells.…”

Section: Discussionmentioning

confidence: 95%

“…The RIBE causes cell death and chromosomal abnormalities in non-irradiated cells surrounding the irradiated area [1,27,28]. Irradiated cells also express COX-2, which synthesizes PGE2, a signaling molecule that promotes cell survival [29].…”

Section: Discussionmentioning

confidence: 99%

“…Taking advantage of microbeams, we clearly show the promotion of DNA damage repair in irradiated A549 cells through the GJIC pathway [13]. In addition, there is much evidence that proves that bystander molecules contribute to cancer development, progression, and resistance [27,28]. Therefore, we hypothesized that RIBE-induced COX-2 expression is one of the reasons for radioresistance in cancer therapy.…”

Section: Introductionmentioning

confidence: 94%

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The COX-2/PGE2 Response Pathway Upregulates Radioresistance in A549 Human Lung Cancer Cells through Radiation-Induced Bystander Signaling

Kobayashi,

Hiroyama,

Mamiya

et al. 2023

Biology

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This study aimed to determine the mechanism underlying the modulation of radiosensitivity in cancer cells by the radiation-induced bystander effect (RIBE). We hypothesized that the RIBE mediates cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2) in elevating radioresistance in unirradiated cells. In this study, we used the SPICE-QST microbeam irradiation system to target 0.07–0.7% cells by 3.4-MeV proton microbeam in the cell culture sample, such that most cells in the dish became bystander cells. Twenty-four hours after irradiation, we observed COX-2 protein upregulation in microbeam-irradiated cells compared to that of controls. Additionally, 0.29% of the microbeam-irradiated cells exhibited increased cell survival and a reduced micronucleus rate against X-ray irradiation compared to that of non-microbeam irradiated cells. The radioresistance response was diminished in both cell groups with the hemichannel inhibitor and in COX-2-knockout cells under cell-to-cell contact and sparsely distributed conditions. The results indicate that the RIBE upregulates the cell radioresistance through COX-2/PGE2 intercellular responses, thereby contributing to issues, such as the risk of cancer recurrence.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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The COX-2/PGE2 Response Pathway Upregulates Radioresistance in A549 Human Lung Cancer Cells through Radiation-Induced Bystander Signaling

Kobayashi,

Hiroyama,

Mamiya

et al. 2023

Biology

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“…In addition, so called "rescue effects" of irradiated cells have been observed, including retro-signaling of non-irradiated cells (»RIRE»)--i.e., in co-cultures unirradiated bystander cells assist irradiated cells via intercellular signal feedback, resulting in less cytotoxicity (apoptosis) and also in less MN formation in irradiated NHLF cells [238,239]. For example, bystander NHLF cells rescued cancer cells: HeLa cells exposed to 200 and 400 mGy of α-rays could be revitalized in co-culture with non-irradiated lung fibroblasts (NHLF).…”

Section: Long Distance Ntes: Abscopal Effectsmentioning

confidence: 99%

Low-Dose Non-Targeted Effects and Mitochondrial Control

Averbeck

2023

IJMS

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Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal effects have also been observed at high doses of IR) relevant to antitumor radiation therapy. IR is inducing NTE involving intracellular and extracellular signaling, which may lead to short-ranging bystander effects and distant long-ranging extracellular signaling abscopal effects. Internal and “spontaneous” cellular stress is mostly due to metabolic oxidative stress involving mitochondrial energy production (ATP) through oxidative phosphorylation and/or anaerobic pathways accompanied by the leakage of O2− and other radicals from mitochondria during normal or increased cellular energy requirements or to mitochondrial dysfunction. Among external stressors, ionizing radiation (IR) has been shown to very rapidly perturb mitochondrial functions, leading to increased energy supply demands and to ROS/NOS production. Depending on the dose, this affects all types of cell constituents, including DNA, RNA, amino acids, proteins, and membranes, perturbing normal inner cell organization and function, and forcing cells to reorganize the intracellular metabolism and the network of organelles. The reorganization implies intracellular cytoplasmic-nuclear shuttling of important proteins, activation of autophagy, and mitophagy, as well as induction of cell cycle arrest, DNA repair, apoptosis, and senescence. It also includes reprogramming of mitochondrial metabolism as well as genetic and epigenetic control of the expression of genes and proteins in order to ensure cell and tissue survival. At low doses of IR, directly irradiated cells may already exert non-targeted effects (NTE) involving the release of molecular mediators, such as radicals, cytokines, DNA fragments, small RNAs, and proteins (sometimes in the form of extracellular vehicles or exosomes), which can induce damage of unirradiated neighboring bystander or distant (abscopal) cells as well as immune responses. Such non-targeted effects (NTE) are contributing to low-dose phenomena, such as hormesis, adaptive responses, low-dose hypersensitivity, and genomic instability, and they are also promoting suppression and/or activation of immune cells. All of these are parts of the main defense systems of cells and tissues, including IR-induced innate and adaptive immune responses. The present review is focused on the prominent role of mitochondria in these processes, which are determinants of cell survival and anti-tumor RT.

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Radiation-Induced Rescue Effect: Insights from Microbeam Experiments

Cited by 2 publications

References 95 publications

The COX-2/PGE2 Response Pathway Upregulates Radioresistance in A549 Human Lung Cancer Cells through Radiation-Induced Bystander Signaling

The COX-2/PGE2 Response Pathway Upregulates Radioresistance in A549 Human Lung Cancer Cells through Radiation-Induced Bystander Signaling

Low-Dose Non-Targeted Effects and Mitochondrial Control

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