Epigallocatechin‑3‑gallate inhibits self‑renewal ability of lung cancer stem‑like cells through inhibition of CLOCK

Abstract

circadian rhythm plays an important role in diverse physiological processes. Abnormal expression of circadian rhythm genes is associated with increased risk of disease, including different types of cancer. The cancer stem cell (cSc) hypothesis suggests that there is a small subset of stem-like cells within tumors that are responsible for tumor initiation. However, the biological effect of circadian rhythm on cScs remains largely unknown. Studies have highlighted that the circadian rhythm protein cLOcK controls key aspects of various diseases. In the present study, lung cancer stem-like cells were successfully enriched using a sphere formation assay. Next, it was observed that cLOcK mRNA and protein expression levels in the A549 and H1299 sphere cells were notably increased compared with those in the corresponding parental cells. In addition, flow cytometry was performed to isolate cd133+ cells and, consistently, cLOcK expression was also found to be markedly upregulated in cd133+ lung cancer cells. Subsequently, to determine the effect of cLOcK on lung cancer stem cells in detail, cLOcK was knocked down using targeted short inhibiting RNA and the results demonstrated that the sphere-forming ability of the A549 and H1299 cell lines was reduced. In addition, cSc-like properties, including.