Abstract
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.
Highlights
Radiotherapy is an important method for malignant tumor treatment
Our study shows that GEN treatment inhibits cytoplasmic translocation of Bcl-xL in non-small cell lung cancer (NSCLC) cells, and the level of cytoplasmic Bcl-xL was negatively correlated with radiosensitivity in NSCLC
GEN is an isoflavone isolated from soy, and previous reports have highlighted that GEN can enhance the efficacy of radiotherapy in numerous tumor types
Summary
Radiotherapy is an important method for malignant tumor treatment. radiation therapy often causes normal tissue injury, and many types of cancer show resistance to radiation therapy[1,2]. GEN is the main isoflavone component in soybeans; it can significantly enhance the radiosensitivity of tumor cells[3], and it attenuates inflammatory injuries in normal tissue caused by ionizing radiation (IR)[4] These anti-tumor effects of GEN were identified in both in vitro and in clinical cases of a wide variety of cancer types, including prostate cancer, breast cancer, colon cancer, gastric cancer, lung cancer, pancreatic cancer, and lymphoma[5,6,7,8]. Studies show that a combination treatment of IR and a Bcl-xL inhibitor exerts a synergistic effect by activating the Bak-apoptosis pathway in cancer cells that are resistant to oncotherapy[19,20]. We identified that increased autophagy by GEN is due to the promotion of Bcl-xL dissociation from Beclin-1, thereby activating Beclin-1 induced autophagy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
