EGCG regulates CTR1 expression through its pro-oxidative property in non-small-cell lung cancer cells
Chen, Jiang, Zeb, Wu, Xu, Chen, Feng (2020) EGCG regulates CTR1 expression through its pro-oxidative property in non-small-cell lung cancer cells J Cell Physiol (IF: 5.6) 235(11) 7970-7981Abstract
Copper transporter 1 (CTR1) plays an important role in increasing cisplatin intake. Our previous studies showed that CTR1 expression was upregulated by (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, therefore enhanced cisplatin sensitivity in ovary cancer and non-small-cell lung cancer (NSCLC) cells. In the current study in the non-small-cell lung cancer cells, we uncovered a potential mechanism of EGCG-induced CTR1 through its pro-oxidative property. We found that EGCG increased reactive oxygen species (ROS) generation, while in the presence of ROS scavenger N-acetyl-cysteine (NAC), ROS production was eliminated. Changes of CTR1 expression were consistent with the ROS level. Simultaneously, EGCG downregulated ERK1/2 while upregulated lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) through ROS to induce CTR1 expression. Besides, in a nude mouse xenografts model, EGCG treatment raised ROS level, expression of CTR1 and NEAT1 in tumor tissue. Also, ERK1/2 and p-ERK1/2 were suppressed as well. Taken together, these results suggested a novel mechanism that EGCG mediated ROS to regulate CTR1 expression through the ERK1/2/NEAT1 signaling pathway, which provided more possibilities for EGCG as a natural agent in adjuvant therapy of lung cancer.© 2020 Wiley Periodicals, Inc.
Links
http://www.ncbi.nlm.nih.gov/pubmed/31943177http://dx.doi.org/10.1002/jcp.29451
