Epigallocatechin gallate (EGCG), the major biologically active compound in green tea, is a well-known chemoprevention agent. Although several reports have shown that EGCG exerts its anticancer activity by targeting specific cell signaling pathways, the underlying molecular mechanism(s) are only partially understood. In the present study, we report that EGCG had a profound antiproliferative effect on human lung cancer cells. EGCG inhibited anchorage-independent growth and induced cell cycle G0/G1 phase arrest. The mechanism underlying EGCG antitumor potency was mainly dependent on suppression of the EGFR signaling pathway. Short-term EGCG exposure substantially decreased EGF-induced EGFR, AKT and ERK1/2 activation. Moreover, long-term EGCG treatment not only inhibited total and membranous EGFR expression, but also markedly attenuated EGFR nuclear localization and expression of the downstream target gene cyclin D1, indicating that EGCG treatment suppressed EGFR transactivation. Additionally, knockdown of EGFR in lung cancer cells decreased their sensitivity to EGCG. Thus, inhibition of the EGFR signaling pathway may partly contribute to the anticancer activity of EGCG.

Background: Hepcidin is a small secreted peptide that plays a key role in iron metabolism. A high level of hepcidin expression may be implicated in colorectal cancer; however, the relationship between hepcidin and lung cancer has not yet been studied. Methods: Serum hepcidin-25, bone morphogenetic protein (BMP)-2, and interleukin (IL)-6 concentration in 53 patients and 16 non-cancerous individuals was measured by enzyme-linked immune sorbent assay. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was utilized to study the expression of hepcidin mRNA in paired tumor and non-tumor lung tissues in surgical specimens from 65 patients with non small cell lung cancer (NSCLC), as well as in six types of lung cancer cell lines and human bronchial epithelial (HBE) cells. Hepcidin protein expression and cellular localization in NSCLC was determined by immunohistochemistry. Results:The serum hepcidin-25 concentration was higher in patients with NSCLC than in non-cancerous individuals, and was positively correlated with serum BMP2 concentration, but negatively with serum IL-6 levels. Serum hepcidin was also correlated with lymph node metastasis and clinical stage. Hepcidin mRNA expression was higher in cancerous tissues of NSCLC than in normal pulmonary tissues (P = 0.001). Hepcidin mRNA levels in four lung carcinoma cell lines were higher than in HBE cells. Immunohistochemistry showed that hepcidin protein was increased in cancerous tissues of NSCLC. Conclusions: The level of hepcidin expression increased in NSCLC tissue and serum. Serum hepcidin-25 level was associated with lymph node metastasis and tumor clinical stage in patients with NSCLC.

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Current technologies to identify and characterize circulating tumor cells (CTCs) and _ circulating tumor microemboli (CTMs) among hundreds of millions of leukocytes in the bloodstream can be classified into tumor-marker-dependent and -independent technology. Isolation by size of epithelial tumor cells (ISET) is a tumor-marker-independent technology, in which CTCs are isolated by filtration without use of tumor-associated markers, as a result of their large size relative to circulating blood leukocytes. ISET allows cytomorphological, immunocytological, and genetic characterization of CTCs and CTMs. It offers a number of advantages, including retention of cell morphology; non-antigen dependence; amenability of cells to further interrogation by immunolabeling, fluorescence in situ hybridization, and RNA/DNA analysis; ability to isolate CTMs; reliability. Therefore, morphological-analysis-based and antigen-independent ISET methodology can yield more accurate and objective characterization of epithelial-mesenchymal transition. We can evaluate efficacy of _chemotherapy and radiotherapy and other cancer-targeting therapies by using xenografts that are suitable models for mechanistic studies of ISET-isolated CTC/CTM biology. In addition, a new _ISET-based device could be designed to increase sensitivity to CTCs/CTMs greatly and reduce the number of CTCs/CTMs directly during the blood flow, thus decreasing the _possibility of tumor recurrence and metastasis while retaining normal blood cells. This article reviews recent advances and prospects in ISET methodology and provides new insights into ISET methodology, with important implications for the clinical management of cancer patients.