Abstract
The epidermal growth factor receptor (EGFR) is one of the most well-studied molecular targets in non-small cell lung cancer (NSCLC) and tyrosine kinase inhibitors have been shown to be effective in the treatment of advanced NSCLC. Nevertheless, the efficacy of tyrosine kinase inhibitors could be compromised by additional mutations in EGFR and compensatory activations of other pathways. Epigallocatechin-3-gallate (EGCG), the main bioactive molecule in green tea, acts as a tyrosine kinase inhibitor toward cancer cells overexpressing EGFR (wild-type). However, little information has been reported on the effect of EGCG on EGFR with activating mutations. In this study, we evaluated the ability of EGCG to inhibit EGFR signaling activation in three different NSCLC cell lines containing wild-type EGFR or EGFR with additional mutations. The effect on proliferation, apoptosis, migration, and vinculin expression was then studied. Overall, our results demonstrate that EGCG polyphenol inhibits cell proliferation and migration in NSCLC cell lines, although with different efficacy and mechanisms. These data may be of interest for an evaluation of the use of EGCG as an adjunct to NSCLC therapies.
Highlights
Lung cancer is the leading cause of cancer-related death in the world, and nonsmall-cell lung cancer (NSCLC) accounts for 85% of cases, with most patients generally presenting, at the moment of diagnosis, an advanced lung cancer [1]
epidermal growth factor receptor (EGFR) undergoes homo- or heterodimerization with other EGFR family receptors. This leads to the autophosphorylation of its tyrosine residues which serve as specific recruitment sites for downstream signaling molecules including mitogen-activated protein kinase (MAPK), a signal transducer and activator of transcription 3 (STAT3), and mammalian target of rapamycin (Figure 1A)
Our findings show a different sensitivity of non-small cell lung cancer (NSCLC) proliferation toward EGCG treatment (A549 > HCC827 > H1975) (Figure 3) which could be attributed in part to the different ability of EGCG to inhibit EGFR signaling
Summary
Lung cancer is the leading cause of cancer-related death in the world, and nonsmall-cell lung cancer (NSCLC) accounts for 85% of cases, with most patients generally presenting, at the moment of diagnosis, an advanced lung cancer [1]. Many studies have shown that 90% of the NSCLC cases are characterized by overexpression and/or aberrant activation of epidermal growth factor receptor (EGFR) [2,3] which is a cell surface receptor tyrosine kinase to which growth factors selectively bind. EGFR undergoes homo- or heterodimerization with other EGFR family receptors. This leads to the autophosphorylation of its tyrosine residues which serve as specific recruitment sites for downstream signaling molecules including mitogen-activated protein kinase (MAPK), a signal transducer and activator of transcription 3 (STAT3), and mammalian target of rapamycin (mTOR) (Figure 1A). EGFR, once triggered, acts as the initiator of the signal transduction process, stimulating cell growth and cell migration [4,5,6,7]
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