Aqueous extract of Trametes robiniophila murr (Huaier) has been commonly used in China for cancer complementary therapy in recent years; however, the mechanisms of its anticancer effects are largely unknown. In the present study, we aim to investigate its inhibitory effect on both MCF-7 and MDA-MB-231 cells, and explore the possible mechanisms of its anticancer effect. Cell viability and motility were measured by MTT and invasive assays, migration and scratch assays in vitro, respectively. The distribution of cell cycle, PI-Annexin-V staining and Rhodamine 123 assay were analyzed by flow cytometry, and western blot were used to test the apoptotic pathways. We found that Huaier extract could strongly inhibit cell viability of MCF-7 and MDA-MB-231 cells in a time-and dose-dependent manner; however, MDA-MB-231 cells showed more susceptibility to the treatment. Furthermore, cell invasiveness and migration were also suppressed with exposure to Huaier extract. We also indicated that Huaier could induce G0/ G1 cell-cycle arrest, p53 accumulation and activation selectively in MCF-7 cells. Inspiringly, the PI-Annexin-V staining assay and western blot analysis confirmed cell apoptosis executed by caspase-3. Decreased mitochondrial membrane potential by Rhodamine 123 assay and down-regulation of Bcl-2 and up-regulation of BCL2-associated X protein (BAX) indicated that Huaier induced apoptosis through the mitochondrial pathway. Caspase activation during Huaier-induced apoptosis was confirmed by pan-caspase inhibitor, Z-VAD-fmk. As expected, the inhibitor decreased Huaier-induced apoptosis in both cell lines. Based on our findings, Huaier can induce cell apoptosis in both ER-positive and ER-negative breast cancer cell lines and is an effective complementary agent for breast cancer treatment. (Cancer Sci 2010; 101: 2375-2383 W orldwide, it is estimated that more than 1 million women are diagnosed with breast cancer every year, and it accounts for approximately 410 000 deaths per year.( 1) Breast cancer is already the leading cause of cancer in southeast Asian women, and is second only to gastric cancer in east Asian women.(2) In some areas of China, the incidence of breast cancer is increasing by 5% per year, greater than that of the worldwide rate.(3) However, compared with other carcinomas, breast cancer has a better prognosis and over 5 million successful survivors comprise nearly 23% of the total cancer survivors in the USA. Although the 5-year survival is estimated at 98% and 94% for stage 1 and 2 localized disease, (4) respectively, the therapeutic options for advanced-stage breast cancers are still fairly limited.(5)

Rapid proliferation and metastasis of breast cancers resulted in poor prognosis in clinic. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in tumor progression. In this study, we aimed to determine the roles and mechanisms of lncRNA–cell division cycle 6 (CDC6) in regulating proliferation and metastasis of breast cancer. Clinically, lncRNA–CDC6 was highly expressed in tumor tissues and was positively correlated with clinical stages of breast cancers. Functionally, the ectopic expression of lncRNA–CDC6 promoted proliferation via regulation of G1 phase checkpoint, and further promoting the migration capability. Moreover, lncRNA–CDC6 could function as competitive endogenous RNA (ceRNA) via directly sponging of microRNA‐215 (miR‐215), which further regulating the expression of CDC6. Taken together, our results proved that lncRNA–CDC6 could function as ceRNA and promote the proliferation and metastasis of breast cancer cells, which provided a novel prognostic marker for breast cancers in clinic.

Delay in diagnosis and treatment predicts worse clinical outcomes. Improvement of medical service in rural areas, especially for premenopausal women, can decrease delays and benefit breast cancer patients.

The epithelial-mesenchymal transition (EMT) is a process in which polarized epithelial cells are converted into motile mesenchymal cells. During cancer development, EMT is conducive to tumor dissemination and metastatic spread. While overexpression of metadherin (MTDH) in breast cancer cell lines and tissues has been found to be associated with aggressive tumor behavior, its precise role in invasion and metastasis is largely unknown. Here we report that MTDH overexpression could significantly enhance the invasion and migration of breast cancer cells by inducing EMT. Metadherin overexpression led to upregulation of mesenchymal marker fibronectin, downregulation of epithelial marker E-cadherin, and the nuclear accumulation of beta-catenin. Also, transcription factors Snail and Slug were upregulated in breast cancer cells overexpressing MTDH. Overexpression of MTDH enhanced the invasiveness and migration ability of breast cancer cells in vitro. In addition, overexpression of MTDH led to increased acquisition of CD44 + ⁄ CD24 ) ⁄ low markers that are characteristic of breast cancer stem cells. We also showed that NF-kappa was involved in the expression of EMT-related markers. Taken together, our results suggest that MTDH could promote EMT in breast cancer cells in driving the progression of their aggressive behavior. (Cancer Sci 2011; 102: 1151-1157 B reast cancer has become the most common malignancy in women around the world. Each year there are over 1 million women diagnosed with breast cancer, with approximately 400 000 deaths.(1) Whereas a more sophisticated combination of surgery, chemotherapy, radiotherapy and endocrine therapy has led to improvements in disease-free survival and overall survival in general, invasion and metastasis remain the main obstacles in the effective treatment of this disease. Therefore, more attention is being paid to unraveling the molecular mechanisms leading to invasive and metastatic dissemination of carcinoma cells.Epithelial to mesenchymal transition (EMT) is a morphogenetic process in which cells undergo a developmental switch from a polarized epithelial phenotype to a highly motile mesenchymal phenotype.(2) It is characterized by the loss of cell-cell adhesion molecules (such as E-cadherin), downregulation of epithelial differentiation markers (CK-18) and transcriptional induction of mesenchymal markers (such as vimentin and fibronectin).(3) Epithelial to mesenchymal transition has been considered to be essential in embryonic development, organ fibrosis, tumor cell migration and the evasion of apoptosis.(4-10) Several transcription factors including Snail, Slug and Twist have been reported to induce EMT by repressing E-cadherin transcription. (8,9) In addition, recent studies have shown that the population of breast cancer cells with the CD44 + ⁄ CD24) ⁄ low phenotype can be expanded by EMT, Twist overexpression or exposure to transforming growth factor beta, (11) and that the CD44 + ⁄ CD24 ) ⁄ low cells exhibited enhanced the invasive properties in breast cancer cells. (12,1...

BackgroundBreast cancer is the most prevalent cancer in women worldwide and metastatic breast cancer has very poor prognosis. Inflammation has been implicated in migration and metastasis of breast cancer, although the exact molecular mechanism remains elusive.Principal FindingsWe show that the pro-inflammatory endotoxin Lipopolysaccharide (LPS) upregulates the expression of Metadherin (MTDH), a recently identified oncogene, in a number of breast cancer lines. Stable knockdown of MTDH by shRNA in human breast MDA-MB-231 cells abolishes LPS-induced cell migration and invasion as determined by several in vitro assays. In addition, knockdown of MTDH diminishes Nuclear Factor-kappa B (NF-κB) activation by LPS and inhibited LPS-induced IL-8 and MMP-9 production.ConclusionsThese results strongly suggest that MTDH is a pivotal molecule in inflammation-mediated tumor metastasis. Since NF-κB, IL-8 and MMP-9 play roles in LPS-induced invasion or metastasis, the mechanism of MTDH-promoted invasion and metastasis may be through the activation of NF-κB, IL-8 and MMP-9, also suggesting a role of MTDH in regulating both inflammatory responses and inflammation-associated tumor invasion. These findings indicate that MTDH is involved in inflammation-induced tumor progression, and support that MTDH targeting therapy may hold promising prospects in treating breast cancer.