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Radiation-induced autophagy contributes to cell death and induces apoptosis partly in malignant glioma cells.
- Source :
-
Cancer research and treatment [Cancer Res Treat] 2015 Apr; Vol. 47 (2), pp. 221-41. Date of Electronic Publication: 2014 Aug 29. - Publication Year :
- 2015
-
Abstract
- Purpose: Radiation-induced autophagy has been shown to play two different roles, in malignant glioma (MG) cells, cytocidal or cytoprotective. However, neither the role of radiation-induced autophagy for cell death nor the existence of autophagy-induced apoptosis, a well-known cell-death pathway after irradiation, has been verified yet.<br />Materials and Methods: We observed both temporal and dose-dependent response patterns of autophagy and apoptosis to radiation in MG cell lines. Additionally, we investigated the role of autophagy in apoptosis through knockdown of autophagy-related proteins.<br />Results: Autophagic activity measured by staining of acidic vesicle organelles and Western blotting of LC-3 protein increased in proportion to radiation dose from day 1 to 5 after irradiation. Apoptosis measured by annexin-V staining and Western blotting of cleaved poly(ADP-ribose) polymerase demonstrated relatively late appearance 3 days after irradiation that increased for up to 7 days. Blocking of pan-caspase (Z-VAD-FMK) did not affect apoptosis after irradiation, but silencing of Atg5 effectively reduced radiation-induced autophagy, which decreased apoptosis significantly. Inhibition of autophagy in Atg5 knockdown cells was shown to be beneficial for cell survival. Stable transfection of GFP-LC3 cells was observed after irradiation. Annexin-V was localized in cells bearing GFP-LC3 punctuated spots, indicating autophagy in immunofluorescence. Some of these punctuated GFP-LC3 bearing cells formed conglomerated spots and died in final phase.<br />Conclusion: These findings suggest that autophagy appears earlier than apoptosis after irradiation and that a portion of the apoptotic population that appears later is autophagy-dependent. Thus, autophagy is a pathway to cell death after irradiation of MG cells.
Details
- Language :
- English
- ISSN :
- 1598-2998
- Volume :
- 47
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer research and treatment
- Publication Type :
- Academic Journal
- Accession number :
- 25410762
- Full Text :
- https://doi.org/10.4143/crt.2013.159