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Cited by 523

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Blocked Autophagy Sensitizes Resistant Carcinoma Cells to Radiation Therapy

Apel, Anja, Herr, Ingrid, Schwarz, Heinz, Rodemann, H. Peter, Mayer, Andreas·2008·Cancer Research

Abstract

Autophagy or “self eating” is frequently activated in tumor cells treated with chemotherapy or irradiation. Whether autophagy represents a survival mechanism or rather contributes to cell death remains controversial. To address this issue, the role of autophagy in radiosensitive and radioresistant human cancer cell lines in response to γ-irradiation was examined. We found irradiation-induced accumulation of autophagosomes accompanied by strong mRNA induction of the autophagy-related genes beclin 1, atg3, atg4b, atg4c, atg5, and atg12 in each cell line. Transduction of specific target-siRNAs led to down-regulation of these genes for up to 8 days as shown by reverse transcription-PCR and Western blot analysis. Blockade of each autophagy-related gene was associated with strongly diminished accumulation of autophagosomes after irradiation. As shown by clonogenic survival, the majority of inhibited autophagy-related genes, each alone or combined, resulted in sensitization of resistant carcinoma cells to radiation, whereas untreated resistant cells but not sensitive cells survived better when autophagy was inhibited. Similarly, radiosensitization or the opposite was observed in different sensitive carcinoma cells and upon inhibition of different autophagy genes. Mutant p53 had no effect on accumulation of autophagosomes but slightly increased clonogenic survival, as expected, because mutated p53 protects cells by conferring resistance to apoptosis. In our system, short-time inhibition of autophagy along with radiotherapy lead to enhanced cytotoxicity of radiotherapy in resistant cancer cells. [Cancer Res 2008;68(5):1485–94]

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Metadata

Authors
Apel, A., Herr, I., Schwarz, H., Rodemann, H. P., & Mayer, A.
Venue
Cancer Research
Published
2008-03-01
Volume
68
Issue
5
Pages
1485-1494
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2103596198
Cited by
523
References
8
FWCI
17.52
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Blocked Autophagy Sensitizes Resistant Carcinoma Cells to Radiation Therapy. https://app.cochat.ai/papers/10.1158/0008-5472.can-07-0562
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Apel, A., Herr, I., Schwarz, H., Rodemann, H. P., & Mayer, A. (2008). Blocked Autophagy Sensitizes Resistant Carcinoma Cells to Radiation Therapy. Cancer Research. https://doi.org/10.1158/0008-5472.can-07-0562

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