Genistein promotes ionizing radiation-induced cell death by reducing cytoplasmic Bcl-xL levels in non-small cell lung cancer

Genistein (GEN) has been previously reported to enhance the radiosensitivity of cancer cells; however, the detailed mechanisms remain unclear. Here, we report that GEN treatment inhibits the cytoplasmic distribution of Bcl-xL and increases nuclear Bcl-xL in non-small cell lung cancer (NSCLC). Intere...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-01, Vol.8 (1), p.328-328, Article 328
Main Authors: Zhang, Zhimin, Jin, Feng, Lian, Xiaojuan, Li, Mengxia, Wang, Ge, Lan, Baohua, He, Hao, Liu, Guo-Dong, Wu, Yan, Sun, Guiyin, Xu, Cheng-Xiong, Yang, Zhen-Zhou
Format: Article
Language:English
Subjects:
Apoptosis
Autophagy
Bcl-x protein
Cell death
DNA damage
Genistein
I.R. radiation
Ionizing radiation
Lung cancer
Non-small cell lung carcinoma
Phagocytosis
Radiosensitivity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Genistein (GEN) has been previously reported to enhance the radiosensitivity of cancer cells; however, the detailed mechanisms remain unclear. Here, we report that GEN treatment inhibits the cytoplasmic distribution of Bcl-xL and increases nuclear Bcl-xL in non-small cell lung cancer (NSCLC). Interestingly, our in vitro data show that ionizing radiation IR treatment significantly increases IR-induced DNA damage and apoptosis in a low cytoplasmic Bcl-xL NSCLC cell line compared to that of high cytoplasmic Bcl-xL cell lines. In addition, clinical data also show that the level of cytoplasmic Bcl-xL was negatively associated with radiosensitivity in NSCLC. Furthermore, we demonstrated that GEN treatment enhanced the radiosensitivity of NSCLC cells partially due to increases in Beclin-1-mediated autophagy by promoting the dissociation of Bcl-xL and Beclin-1. Taken together, these findings suggest that GEN can significantly enhance radiosensitivity by increasing apoptosis and autophagy due to inhibition of cytoplasmic Bcl-xL distribution and the interaction of Bcl-xL and Beclin-1 in NSCLC cells, respectively.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-18755-3