Radiation induces apoptosis primarily through the intrinsic pathway in mammalian cells.

Abstract

Radiation-induced tumor cells death is the theoretical basis of tumor radiotherapy. Death signaling disorder is the most important factor for radioresistance. However, the signaling pathway(s) leading to radiation-triggered cell death is (are) still not completely known. To better understand the cell death signaling induced by radiation, the immortalized mouse embryonic fibroblast (MEF) deficient in "initiator" caspases, "effector" caspases or different Bcl-2 family proteins together with human colon carcinoma cell HCT116 were used. Our data indicated that radiation selectively induced the activation of caspase-9 and caspase-3/7 but not caspase-8 by triggering mitochondrial outer membrane permeabilization (MOMP). Importantly, the role of radiation in MOMP is independent of the activation of both "initiator" and "effector" caspases. Furthermore, both proapoptotic and antiapoptotic Bcl-2 family proteins were involved in radiation-induced apoptotic signaling. Overall, our study indicated that radiation specifically triggered the intrinsic apoptotic signaling pathway through Bcl-2 family protein-dependent mitochondrial permeabilization, which indicates targeting mitochondria is a promising strategy for cancer radiotherapy.

• Authors: Xianbin Cao, Pengbo Wen, Yanfang Fu, Yang Gao, Xiaojing Qi, Bin Chen, Yinping Tao, Lijun Wu, An Xu, Huayi Lu, Guoping Zhao
• Journal: Cellular signalling (Cell Signal) Vol. 62 Pg. 109337 (10 2019) ISSN: 1873-3913 [Electronic] England
• PMID: 31173879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• BCL2 protein, human
• Proto-Oncogene Proteins c-bcl-2
• Caspase 3
• Caspase 7
• Caspase 9

Topics

• Animals
• Apoptosis (genetics, radiation effects)
• Caspase 3 (genetics)
• Caspase 7 (genetics)
• Caspase 9 (genetics)
• Cell Death
• Fibroblasts (radiation effects)
• HCT116 Cells
• Humans
• Mice
• Mitochondria (genetics, radiation effects)
• Mitochondrial Transmembrane Permeability-Driven Necrosis (radiation effects)
• Neoplasms (genetics, pathology, radiotherapy)
• Proto-Oncogene Proteins c-bcl-2 (genetics)