EGCG regulates CTR1 expression through its pro-oxidative property in non-small-cell lung cancer cells.

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 generation, while in the presence of scavenger N-acetyl-cysteine (NAC), duanyu1670 production was eliminated. Changes of CTR1 expression were consistent with the duanyu1670 level. Simultaneously, EGCG downregulated ERK1/2 while upregulated lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) through duanyu1670 to induce CTR1 expression. Besides, in a nude mouse xenografts model, EGCG treatment raised duanyu1670 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 duanyu1670 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.

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