Autophagy contributes to resistance of tumor cells to ionizing radiation

Chaachouay, Hassan; Ohneseit, Petra; Toulany, Mahmoud; Kehlbach, Rainer; Multhoff, Gabriele; Rodemann, H. Peter

doi:10.1016/j.radonc.2011.06.002

Cited by 235 publications

(185 citation statements)

References 46 publications

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“…This is of particular importance for investigations into the role of radiation-induced autophagy in cellular radiation sensitivity or resistance. 718,719 Most other inhibitory drugs act at post-sequestration steps. These types of agents have been used in many experiments to both inhibit endogenous protein degradation and to increase the number of autophagic compartments.…”

Section: 696mentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy

Klionsky¹,

Abdalla²,

Abeliovich³

et al. 2012

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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

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Section: 696mentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy

Klionsky¹,

Abdalla²,

Abeliovich³

et al. 2012

Self Cite

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“…11 Other groups have previously investigated the potential of CNPs to protect normal cells against radiation-induced damage. 12 Apoptosis is the main mode of radiation-induced cell death, but another important mechanism is autophagy, 13 a conserved process of protein degradation in which doublemembrane vesicles known as autophagosomes engulf intracellular contents such as endoplasmic reticulum, mitochondria, and ribosomes and fuse with lysosomes for cargo degradation.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Chen¹,

Zhang²,

Hu³

et al. 2015

IJN

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Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

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“…However, in cancer therapy, the role of autophagy is paradoxical. In certain studies, autophagy appeared to function as a protective mechanism against cellular stress (33,34).…”

Section: Discussionmentioning

confidence: 99%

Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models

Zhao¹,

Zhao-peng

et al. 2016

Oncology Letters

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Autophagy contributes to resistance of tumor cells to ionizing radiation

Cited by 235 publications

References 46 publications

Guidelines for the use and interpretation of assays for monitoring autophagy

Guidelines for the use and interpretation of assays for monitoring autophagy

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models

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Autophagy contributes to resistance of tumor cells to ionizing radiation

Cited by 235 publications

References 46 publications

Guidelines for the use and interpretation of assays for monitoring autophagy

Guidelines for the use and interpretation of assays for monitoring autophagy

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in&nbsp;breast cancer cells

Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models

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Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells