title: EGCG inhibits the invasion of highly invasive CL1-5 lung cancer cells through suppressing MMP-2 expression via JNK signaling and induces G2/M arrest.
abstract: Tumor metastasis is the main obstacle to the treatment of lung cancer. According to previous findings, matrix metalloproteinase-2 (MMP-2) is closely correlated with metastatic potential in lung cancer. This study showed that epigallocatechin-3-gallate (EGCG), a natural polyphenol in green tea, is a potent inhibitor of MMP-2 expression. EGCG effectively suppressed the invasion and migration of highly invasive CL1-5 lung cancer cells. Gelatin zymography, Western blot analysis, and RT-PCR were used to investigate the effects of EGCG on MMP-2 expression. The effects of EGCG on cell cycle and apoptosis were determined by flow cytometry analysis. To investigate the effects of EGCG on cell migration and cell invasion, Transwell migration/invasion assays were used. EGCG downregulated MMP-2 expression at the transcriptional level in CL1-5 cells. Moreover, the treatment of CL1-5 cells with EGCG caused downregulation of c- Jun N-terminal kinase (JNK), resulting in repression of the translocation of transcriptional factors, Sp1, and NF-κB, from the cytosol into the nucleus. In addition, EGCG significantly and synergistically enhanced the antitumor effects of the clinical drug, docetaxel, in CL1-5 cells. Further, EGCG induced G2/M arrest at dosages higher than those of suppression in cell invasion in CL1-5 cells. These results reveal that EGCG might decrease MMP-2 mRNA expression through JNK signaling, further suggesting that a combination of EGCG and docetaxel may be a promising strategy to help increase the efficacy of docetaxel in suppressing metastasis in lung cancer cells. In addition, EGCG may suppress cell proliferation in CL1-5 cells through inducing G2/M arrest.
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yea-Tzy
authors.initials: YT
authors.lastname: Deng
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Lin
mesh_terms: D016588:Anticarcinogenic Agents; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D013662:Tea
chemical_list: D016588:Anticarcinogenic Agents; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2