EGCG regulates the cross-talk between JWA and topoisomerase IIα in non-small-cell lung cancer (NSCLC) cells

(-)-epigallocatechin-3-gallate (EGCG) is a well-known cancer chemopreventive agent. The potential mechanisms include regulation of multiple molecules. Carcinogenesis in lung cancer is related to the imbalance of tumor suppressor and oncogene. JWA is a structurally novel microtubule-binding protein and is a potential tumor suppressor. DNA topoisomerase II alpha is a nuclear enzyme that governs DNA topology and is usually highly expressed in many types of cancer. It serves as a target of anticancer drugs. In the current study, the regulation of JWA and topoisomerase II alpha by EGCG, and thereafter the mutual interaction between them was investigated. The results revealed that EGCG up-regulated JWA while decreased topoisomerase II alpha expression in both human non-small cell lung cancer (NSCLC) cells and an NSCLC xenograft mice model. There was a negative correlation between JWA and topoisomerase II alpha in NSCLC as well as in human NSCLC tissue specimens. Topoisomerase II alpha overexpression reduced JWA at the translational level. Meanwhile, JWA-induced topoisomerase II alpha degradation was regulated both in the transcriptional and post-translational level. Interestingly, JWA and topoisomerase II alpha regulated each other in the cells arrested in G2/M. Furthermore, JWA and topoisomerase II alpha synergistically affected NCI-H460 cells invasion. These results may serve a novel mechanism for cancer prevention.