High-LET radiation combined with oxaliplatin induce autophagy in U-87 glioblastoma cells

Benzina, Sami; Altmeyer, Anaïs; Malek, Faten; Dufour, Patrick; Denis, Jean‐Marc; Gueulette, John; Bischoff, Pierre

doi:10.1016/j.canlet.2008.01.023

Cited by 29 publications

(15 citation statements)

References 17 publications

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“…Concordant with these findings, we observed greater than 10% steatotic hepatocytes in 32.8% of the patients and vascular lesions in 44.3%; only one patient had a completely normal liver parenchyma. Anticancer drugs have also been described to induce autophagy [22,23], an observation that could explain the low levels of autophagic vacuoles, as assessed by transmission electron microscopy, that we observed in liver biopsies before IP or I/R.…”

Section: Discussionmentioning

confidence: 74%

Concurrent induction of necrosis, apoptosis, and autophagy in ischemic preconditioned human livers formerly treated by chemotherapy

Domart

Esposti

Sebagh

et al. 2009

Journal of Hepatology

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Section: Discussionmentioning

confidence: 74%

Concurrent induction of necrosis, apoptosis, and autophagy in ischemic preconditioned human livers formerly treated by chemotherapy

Domart

Esposti

Sebagh

et al. 2009

Journal of Hepatology

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“…Inhibition of autophagy induction using small interfering (si)RNA targeted to beclin-1 and ATG7 significantly enhanced the effects of chemotherapeutic drugs, and reduced the recovery of drug-treated cells. Autophagy is frequently observed in cancer cells following exposure to ionizing radiation, and inhibition of autophagy has been shown to precipitate radiation-induced cell death (30). Lomonaco et al (31) previously demonstrated that γ-radiation activated autophagy and inhibition of autophagy significantly increased the radiosensitivity of glioma cells and glioma stem cells.…”

Section: Discussionmentioning

confidence: 99%

Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer

Chen

Xiao-hong

Guo

et al. 2015

Molecular Medicine Reports

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Radiotherapy is an effective treatment for esophageal cancer; however, tumor resistance to radiation remains a major biological problem. The present study aimed to investigate whether inhibition of autophagy may decrease overall tumor resistance to radiation. The effects of the autophagy inhibitor 3-methyladenine (3-MA) on radiosensitivity were tested in the EC9706 human esophageal squamous cell carcinoma cell line by colony formation assay. Furthermore, the synergistic cytotoxic effects of 3-MA and radiation were assessed in a tumor xenograft model in nude mice. Mechanistic studies were performed using flow cytometry, immunohistochemistry and western blot analysis. The results of the present study demonstrated that radiation induced an accumulation of autophagosomes and 3-MA effectively inhibited radiation-induced autophagy. Inhibition of autophagy was shown to significantly increase the radiosensitivity of the tumors in vitro and in vivo. The enhancement ratio of sensitization in EC9706 cells was 1.76 when the cells were treated with 10 mM 3-MA, alongside ionizing radiation. In addition, autophagy inhibition increased apoptosis and reduced tumor cell proliferation. The combination of radiation and autophagy inhibition resulted in a significant reduction in tumor volume and vasculature in the murine model. The present study demonstrated in vitro and in vivo that radiation-induced autophagy has a protective effect against cell death, and inhibition of autophagy is able to enhance the radiosensitivity of esophageal squamous cell carcinoma.

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“…It seems that autophagic cell death accounts for the cytotoxicity and may be correlated to the amount and severity of DNA damage in glioma cells. 68 Ionizing radiation inhibits cell proliferation in a dose-dependent manner in both human malignant glioma cells (U87-MG) and cells with a constitutively active form of epidermal growth factor receptor (U87MGΔEGFR), but the number of viable cells of each cell line did not decrease, even after the administration of 10 Gy. 69 One reason for radioresistance is that 10-Gy irradiation transiently increased the levels of phosphorylated Akt and phosphorylated p70S6K in both U87-MG and U87MGDEGFR cells.…”

Section: B I O S C I E N C E D O N O T D I S T R I B U T Ementioning

confidence: 97%

“…It seems that the lost DNA-PKcs play an important role in radiation-induced autophagy and cell death in malignant gliomas. 67 Benzina et al 68 observed that high-LET radiation alone, or combined with oxaliplatin, induces autophagic cell death and decreases tumor growth in glioblastoma cells U-87 and in mice xenografts. In the same study, the DNA double strand break formation and the reduction of the DNA repair process were more intense in the cotreated cells, as compared to irradiated cells alone.…”

Section: B I O S C I E N C E D O N O T D I S T R I B U T Ementioning

confidence: 99%

“…In the same study, the DNA double strand break formation and the reduction of the DNA repair process were more intense in the cotreated cells, as compared to irradiated cells alone. 68 Furthermore, when oxaliplatin was combined with irradiation, the levels of apoptosis were reduced as compared to irradiation alone. It seems that autophagic cell death accounts for the cytotoxicity and may be correlated to the amount and severity of DNA damage in glioma cells.…”

Section: B I O S C I E N C E D O N O T D I S T R I B U T Ementioning

confidence: 99%

See 1 more Smart Citation

Radiation-induced autophagy in normal and cancer cells: Towards novel cytoprotection and radio-sensitization policies?

Zois¹,

Koukourakis²

2009

Autophagy

124

101

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Autophagy or Type II programmed cell death (PCD) is a major intracellular pathway for the degradation and recycling of proteins, ribosomes and entire organelles. The role of this pathway in the antitumor effect of radiotherapy and in radiation toxicity is obscure. A complicated machinery of genes and proteins is involved in the regulation of autophagy as a response to a variety of stress factors including hypoxia, nutrient deprivation, cytotoxic agents and radiotherapy. Continuously accumulating data suggest that autophagic response of cancer cells to radiotherapy is a major pathway which, in contrast to apoptosis that leads to death, may lead to either death or cellular survival. A variety of agents have been recognized that induce or block autophagy, directly interfering with the cytotoxic effect of radiotherapy. Simultaneous targeting of autophagy and apoptosis during radiotherapy seems to further augment the antitumor effect. Radiobiology research should focus on the differential effect of fractionation on the induction of autophagy in different tumors and on the manipulation of this with autophagy triggering agents. Whether manipulation of this pathway in normal tissues may be used to confer cytoprotection also deserves thorough investigation. Moreover, the role of pretreatment autophagic indices in tumor cells in predicting radiotherapy and chemotherapy outcome should be examined in translational studies.

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High-LET radiation combined with oxaliplatin induce autophagy in U-87 glioblastoma cells

Cited by 29 publications

References 17 publications

Concurrent induction of necrosis, apoptosis, and autophagy in ischemic preconditioned human livers formerly treated by chemotherapy

Concurrent induction of necrosis, apoptosis, and autophagy in ischemic preconditioned human livers formerly treated by chemotherapy

Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer

Radiation-induced autophagy in normal and cancer cells: Towards novel cytoprotection and radio-sensitization policies?

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