Background: Notch-1 plays a critical role in cell fate decisions by modulating cellular processes under irradiation. Results: Irradiation-induced Notch-1 overexpression promoted survival and EMT in NSCLC, whereas rhamnetin and cirsiliol inhibited these effects via miR-34a-mediated Notch-1 down-regulation. Conclusion: Rhamnetin and cirsiliol suppress Notch-1-mediated radioresistance and EMT phenotypes in NSCLC. Significance: Rhamnetin and cirsiliol can act as novel radiosensitizers by inhibiting radiation-induced Notch-1 signaling.
Radiotherapy is the most significant non‐surgical cancer treatment, however it is restricted by two major problems: radioresistance and normal tissue damage. We focused on radiation‐induced normal cell damage, and are concerned with inflammation as a main limiting factor in the radiotherapy. Psoralidin, a coumestan derivative isolated from the seed of Psoralea corylifolia, has been studied for various biological properties. However, little is known regarding its effects on IR‐induced pulmonary inflammation. The aim of this study is to investigate mechanisms of IR‐induced inflammation and to examine therapeutic mechanisms of psoralidin. We demonstrated that IR‐induced ROS activated COX‐2 and 5‐LOX pathway in HFL‐1 and MRC‐5 cells. Psoralidin inhibited the IR‐induced COX‐2 expression and PGE2 production through regulation of PI3K/Akt and NF‐κB signaling. Also, psoralidin blocked IR‐induced LTB4 production through a direct interaction of psoralidin and FLAP. IR‐induced fibroblast migration was notably attenuated by psoralidin. Moreover, psoralidin suppressed IR‐induced expression of pro‐inflammatory cytokines and ICAM‐1 in vivo. Taken together, our findings reveal a regulatory mechanism of IR‐induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that psoralidin may be useful as a potential radiopreventive agent against radiation‐induced normal tissue injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.