Canonical autophagy does not contribute to cellular radioresistance.

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Marco B E SchaafKasper M A Rouschop

Abstract

(Pre)clinical studies indicate that autophagy inhibition increases response to anti-cancer therapies. Although promising, due to contradicting reports, it remains unclear if radiation therapy changes autophagy activity and if autophagy inhibition changes the cellular intrinsic radiosensitivity. Discrepancies may result from different assays and models through off-target effects and influencing other signaling routes. In this study, we directly compared the effects of genetic and pharmacological inhibition of autophagy after irradiation in human cancer cell lines. Changes in autophagy activity after ionizing radiation (IR) were assessed by flux analysis in eight cell lines. Clonogenic survival, DNA damage (COMET-assay) and H2AX phosphorylation were assessed after chloroquine or 3-methyladenine pretreatment and after ATG7 or LC3b knockdown. IR failed to induce autophagy and chloroquine failed to change intrinsic radiosensitivity of cells. Interestingly, 3-methyladenine and ATG7- or LC3b-deficiency sensitized cancer cells to irradiation. Surprisingly, the radiosensitizing effect of 3-methyladenine was also observed in ATG7 and LC3b deficient cells and was associated with attenuated γ-H2AX formation and DNA damage repair. Our data ...Continue Reading

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Jul 16, 2013·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Marco B E SchaafKasper M A Rouschop
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Aug 15, 2014·Cancer Cell·Hannelore MaesPeter Carmeliet

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Citations

Sep 1, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Hassan ChaachouayH Peter Rodemann
Mar 20, 2016·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Martin OndrejAles Tichy
Aug 9, 2017·Journal of Cancer Research and Clinical Oncology·Yong XinGuan Jiang
Dec 10, 2016·Frontiers in Oncology·Tom G KeulersKasper M A Rouschop
Aug 28, 2020·Radiation Research·Nipa H PatelDavid A Gewirtz
Jan 26, 2017·Oxidative Medicine and Cellular Longevity·Lelin HuJunjie Wang

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