Background: Previous studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms. Methods: NPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot. Results: NPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures. Conclusions: Overall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC), a tumor arising from the epithelial cells of the nasopharynx, is endemic in Southeast Asia and Taiwan. The prognosis of NPC patients with local recurrence and metastasis is poor. Resistance to anoikis is a primary characteristic of tumor cells that metastasize. However, the mechanism through which NPC cells resist anoikis and are able to metastasize has not been fully elucidated. In the present study, the acquisition of anoikis resistance was analyzed in the TW01 and TW06 human NPC cell lines growing under anchorage-independent conditions. A considerable number of TW01 and TW06 cells was found to be resistant to anoikis and exhibited a higher capability of migration and invasion. These anoikis-resistant NPC cells exhibited significantly increased expression of signal transducer and activation of transcription 3 (Stat3) compared with adherent cells. Furthermore, blockade of STAT3 expression by STAT3 inhibitors or STAT3 silencing significant increased anoikis in anoikis-resistant NPC cells. Moreover, silencing STAT3 not only reduced the capacity of NPC cells to resist anoikis, but also reversed their invasive properties. The expression of epithelial‑to-mesenchymal transition‑related proteins and CD44 was also significantly decreased following STAT3 knockdown. The results of the present study established that STAT3 mediates anoikis resistance, with enhanced cell migration and invasion of NPC cells, and that activation of STAT3 may increase metastatic capacity, indicating the crucial role of STAT3 in conferring anoikis resistance and enhanced invasive properties to NPC cells.

Recent studies have shown that cancer stem-like cells (CSCs) within a tumor have the capacity for self-renewal and differentiation, and are associated with an aggressive phenotype and therapeutic resistance. Studies have also associated tumor progression with alterations in the levels of intracellular reactive oxygen species (ROS). In this study, we cultured nasopharyngeal carcinoma (NPC) CSCs in conditions that allowed sphere formation. The resulting sphere cells displayed stemness properties, characteristics of the epithelial–mesenchymal transition (EMT), and increased expression of the CSC surface marker CD44. We further evaluated the association between CD44 expression and EMT marker expression, and any correlation with redox status, in these CSCs. We showed that the EMT in sphere cells is associated with the upregulation of CD44 expression and increased ROS generation, which might promote NPC aggressiveness. We also identified the coexpression of CD44 with the EMT marker N-cadherin in sphere cells, and downregulated CD44 expression after the addition of the antioxidant N-acetyl cysteine. Our results indicate that CD44 plays a role in the EMT phenotype of CSCs in NPC, and suggest its involvement in EMT-associated ROS production. These findings might facilitate the development of a novel therapy for the prevention of NPC recurrence and metastasis.

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Background As both of peripheral arterial disease (PAD) and depression carried a poor prognosis in patients on maintenance hemodialysis (MHD), we investigated the correlation between the ankle-brachial index (ABI), an indicator of subclinical PAD, and symptoms of depression in patients on MHD. Methods One hundred and twenty-nine patients on MHD (75 males and 54 females, mean age 64.8 ± 12 years) were enrolled in this cross-sectional study, which aimed at evaluating the relationship between symptoms of depression and ABI. Demographic as well as clinical and laboratory variables including status of diabetes, chronic hepatitis C infection, dialysis duration, Charlson comorbidity index (CCI), plasma levels of albumin, C-peptide, insulin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin, and lipid profile were obtained. The self-administered beck depression inventory (BDI) was used to determine the presence or absence of symptoms of depression, and depression was defined as a BDI score ≧14. Multivariable-adjusted linear regression models were constructed to confirm the independent association of biologic parameters of symptoms of depression. Significance was defined as P < 0.05. Statistical analyses were performed using SPSS/Windows software (SPSS Science, v. 15.0, Chicago, IL). Results The mode of multivariate analysis showed that diabetes (β = 3.594; P = 0.040), hepatitis C infection (β = 4.057; P = 0.008), levels of serum albumin (β = −5.656; P = 0.024), C-peptide (β = −0.292; P = 0.002), ABI (β = −9.041; P = 0.031), and Ln-transformed hsCRP were significantly associated with BDI. Conclusions Hepatitis C infection, serum levels of albumin, C-peptide, and ABI levels were found to be correlated with BDI (P < 0.05).