Ionizing radiation triggers mitophagy to enhance DNA damage in cancer cells

Ren, Yanxian; Yang, Pengfei; Li, Chenghao; Wang, Weihong; Zhang, Tianyi; Jin, Li; Li, H; Dong, Changfeng; Meng, Wenbo; Zhou, Heng

doi:10.1038/s41420-023-01573-0

Cited by 12 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed variations in the median cell area, both across different cell lines within the same condition and within each cell line across radiation conditions. The median area of the cells increased after irradiation with 10 Gy, which agrees with previously observed cellular enlargement of irradiated cells [Rene and Nardone, 1968;Ronny Sham et al, 2020;Ren et al, 2023]. The UPCISCC131 cell line displayed the most increase in median cell area following irradiation.…”

Section: Resultssupporting

confidence: 90%

RUCova: Removal of Unwanted Covariance in mass cytometry data

Astaburuaga-García,

Sell,

Mutlu

et al. 2024

Preprint

View full text Add to dashboard Cite

High dimensional mass cytometry is confounded by unwanted covariance due to variations in cell size and staining efficiency, making analysis and interpretation challenging.We present RUCova, a novel method designed to address confounding factors in mass cytometry data. RUCova removes unwanted covariance using multivariate linear regression on Surrogates of Unwanted Covariance (SUCs), and Principal Component Analysis (PCA). We exemplify the use of RUCova and show that it effectively removes unwanted covariance while preserving genuine biological signals. Our results demonstrate the efficacy of RUCova in elucidating complex data patterns, facilitating the identification of activated signalling pathways, and improving the classification of important cell populations. By providing a robust framework for data normalization and interpretation, RUCova enhances the accuracy and reliability of mass cytometry analyses, contributing to advancements in our understanding of cellular biology and disease mechanisms. The R package is available onhttps://github.com/molsysbio/RUCova. Detailed documentation, data, and the code required to reproduce the results are available onhttps://doi.org/10.5281/zenodo.10913464. Supplementary material: Available at bioRxiv.

show abstract

Section: Resultssupporting

confidence: 90%

RUCova: Removal of Unwanted Covariance in mass cytometry data

Astaburuaga-García,

Sell,

Mutlu

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…However, there is a disparity in the levels of cath L between the western blot and immunofluorescence results, which may be attributed to mitophagy. A study by Yanxian et al ( 2023) [53] previously demonstrated mitophagy in cells exposed to ionizing radiation, showing a dose-dependent increase in mitophagy. As a result, our hypothesis proposes that the intensified lysotracker red staining in the immunofluorescence images is not solely due to elevated specific cathepsin expression.…”

Section: Discussionmentioning

confidence: 96%

Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells

Abdelaziz,

Hussein,

Kotob

et al. 2023

IJMS

View full text Add to dashboard Cite

Cancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, radiation resistance remains a significant challenge in cancer treatment, limiting its efficacy. Emerging evidence suggests that cathepsin L (cath L) contributes to radiation resistance through multiple mechanisms. In this study, we investigated the role of cath L, a member of the cysteine cathepsins (caths) in radiation sensitivity, and the potential reduction in radiation resistance by using the specific cath L inhibitor (Z-FY(tBu)DMK) or by knocking out cath L with CRISPR/Cas9 in colon carcinoma cells (caco-2). Cells were treated with different doses of radiation (2, 4, 6, 8, and 10), dose rate 3 Gy/min. In addition, the study conducted protein expression analysis by western blot and immunofluorescence assay, cytotoxicity MTT, and apoptosis assays. The results demonstrated that cath L was upregulated in response to radiation treatment, compared to non-irradiated cells. In addition, inhibiting or knocking out cath L led to increased radiosensitivity in contrast to the negative control group. This may indicate a reduced ability of cancer cells to recover from radiation-induced DNA damage, resulting in enhanced cell death. These findings highlight the possibility of targeting cath L as a therapeutic strategy to enhance the effectiveness of RT. Further studies are needed to elucidate the underlying molecular mechanisms and to assess the translational implications of cath L knockout in clinical settings. Ultimately, these findings may contribute to the development of novel treatment approaches for improving outcomes of RT in cancer patients.

show abstract

“…Another study showed that IR damages mitochondria by deforming them and initiates mitophagy in both PANC-1 and SW1990 cells by increasing the levels of the mitophagic sensors Parkin and BNIP3. After a period of 48 h following X-ray irradiation, it was observed that there was a rise in the spatial proximity between the lysosomes and mitochondria in both PANC-1 and SW199 cells [ 204 ]. The effect of high-dose irradiation leads to a decrease in the mitochondrial membrane potential, which correlates with defective protein import.…”

Section: Radiation-induced Cellular Senescencementioning

confidence: 99%

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Ibragimova,

Kussainova,

Aripova

et al. 2024

Cells

View full text Add to dashboard Cite

This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.

show abstract

Ionizing radiation triggers mitophagy to enhance DNA damage in cancer cells

Cited by 12 publications

References 34 publications

RUCova: Removal of Unwanted Covariance in mass cytometry data

RUCova: Removal of Unwanted Covariance in mass cytometry data

Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Contact Info

Product

Resources

About