Crosstalk between autophagy and intracellular radiation response (Review)

Abstract

Abstract. Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca 2+ concentration which activate many signaling pathways to modulate autophagy. Herein we review the role of autophagy in radiation therapy and the potent intracellular autophagic triggers induced by radiation. We aim to provide a more theoretical basis of radiation-induced autophagy, and provide novel targets for developing cytotoxic drugs to increase radiosensitivity. Contents1. Introduction 2. The role of autophagy in radiotherapy 3. DNA damage repair and autophagy 4. Mitochondrial damage and autophagy 5. ER stress and autophagy 6. ROS and autophagy 7. Ceramide and autophagy 8. Ca 2+ and autophagy 9. Targeting autophagy for radiotherapy 10. Conclusion IntroductionRadiotherapy is an effective strategy for the treatment of many kinds of cancer to kill or control the malignant tumor cells. However, its benefits have been limited due to radiation resistance. It is imperative to identify new targets and develop cytotoxic drugs to increase radiosensitivity. Radiosensitization has traditionally been performed with agents known to induce apoptosis. However, recent studies demonstrate autophagy induced by radiation also plays an important role in cancer Crosstalk between autophagy and intracellular radiation response (Review)

The Protective Roles of ROS‐Mediated Mitophagy on 125I Seeds Radiation Induced Cell Death in HCT116 Cells

“…In the initial stage, membrane distant from either the Golgi or ER sequesters cellular components to form autophagosome. At a relatively late stage of autophagy, autophagosome fuses with the lysosome to form an autolysosome, where LC3-II and sequestered cellular components were degraded by lysosomal hydrolytic enzymes [31–33]. There are two causes for the accumulation of LC3-II: one is increase of autophagosome formation and the other is inhibition of the formation of autolysosomes which is the site for degradation of autophagosomes [34].…”

Potentially Functional Variants of ATG16L2 Predict Radiation Pneumonitis and Outcomes in Patients with Non–Small Cell Lung Cancer after Definitive Radiotherapy

“…22 There are two primary opposing functions by radiation-induced autophagy: cytoprotective and cytotoxic. While radiation-induced autophagy often serves as a protective function in cell culture-based studies, it is still unclear to what an extent autophagy may be induced by radiation in human cancer cells, although the function of autophagy in response to radiation is inconsistent.…”

Mechanistic target of rapamycin inhibition with rapamycin induces autophagy and correlative regulation in white shrimp (Litopenaeus vannamei)

“…ATG1 exists in a complex with ATG13 and ATG17. The complex ATG1–ATG13–ATG17 is involved in the early nucleation steps of autophagosome formation (Hu et al., ). Treatment with rapamycin improves ATG1 activation by inhibiting the phosphorylation of ATG1 Ser757 (Kim et al., ).…”