Depression is more common in women with breast cancer than the general population. Selective serotonin reuptake inhibitors (SSRIs), a group of antidepressants, are widely used for the treatment of patients with depression and a range of anxiety-related disorders. The association between the use of antidepressant medication and breast cancer is controversial. In this study, we investigated whether and how SSRIs induce the death of human breast cancer MCF-7 cells. Of the antidepressants tested in this study (amitriptyline, bupropion, fluoxetine, paroxetine, and tianeptine), paroxetine most reduced the viability of MCF-7 cells in a time-and dose-dependent manner. The exposure of MCF-7 cells to paroxetine resulted in mitochondrion-mediated apoptosis, which is assessed by increase in the number of cells with sub-G1 DNA content, caspase-8/9 activation, poly (ADP-ribose) polymerase cleavage, and Bax/Bcl-2 ratio and a reduction in the mitochondrial membrane potential. Paroxetine increased a generation of reactive oxygen species (ROS), intracellular Ca2+ levels, and p38 MAPK activation. The paroxetine-induced apoptotic events were reduced by ROS scavengers and p38 MAPK inhibitor, and the paroxetine’s effect was dependent on extracellular Ca2+ level. Paroxetine also showed a synergistic effect on cell death induced by chemotherapeutic drugs in MCF-7 and MDA-MB-231 cells. Our results showed that paroxetine induced apoptosis of human breast cancer MCF-7 cells through extracellular Ca2+-and p38 MAPK-dependent ROS generation. These results suggest that paroxetine may serve as an anticancer adjuvant to current cancer therapies for breast cancer patients with or without depression.

Increasing antioxidant capacity has been proposed as a promising strategy to prevent cigarette smoke-induced lung diseases. This study tested whether garlic extracts prevented cigarette smoke extract (CSE)-induced cell death in human bronchial smooth muscle cells (HBSMCs). Garlic extracts were prepared from fresh raw garlic (FRG), aged black garlic (ABG) and aged red garlic (ARG). Treatment of HBSMCs with 10% CSE induced cell death accompanied by activation of caspase. Of the garlic extracts, treatment with ARG extract reduced CSE-induced cell death. The combination of ARG extract with CSE attenuated the CSE-induced reduction in glutathione (GSH) content, generation of reactive oxygen species (ROS) and induction of heme oxygenase-1 expression compared with CSE treatment without ARG extract. Furthermore, the combination of L-BSO, a GSH synthesis inhibitor, with ARG and CSE extracts failed to increase the intracellular GSH content and cell viability. Taken together, these results demonstrate that ARG extract reduces CSE-induced cell death by increasing GSH content and reducing ROS generation in HBSMCs.

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Little is known about the biological role of human mammaglobin (hMAM) that is considered as a promising marker for breast cancer. Here, we investigated hMAM's role related to migration and invasion of human breast cancer cells (hBCC). Compared to normal cells, hBCC have high MAM mRNA expression levels. Of the hBCC tested, MAM mRNA expression levels were higher in noninvasive than in invasive cells. Overexpression of hMAM in breast cancer cells decreased migration and invasion, whereas knockdown of hMAM increased both. Taken together, these results suggest that metastasis of hBCC could be controlled by hMAM expression levels.

The proliferation, migration, cytokine release, and contraction of airway smooth muscle cells are key events in the airway remodeling process that occur in lung disease such as asthma, chronic obstruction pulmonary disease, and cancer. These events can be modulated by a number of factors, including cigarette smoke extract (CSE). CSE-induced alterations in the viability, migration, and contractile abilities of normal human airway cells remain unclear. This study investigated the effect of CSE on cell viability, migration, tumor necrosis factor (TNF)-α secretion, and contraction in normal human bronchial smooth muscle cells (HBSMCs). Treatment of HBSMCs with 10% CSE induced cell death, and the death was accompanied by the generation of reactive oxygen species (ROS). CSE-induced cell death was reduced by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, CSE reduced the migration ability of HBSMCs by 75%. The combination of NAC with CSE blocked the CSE-induced reduction of cell migration. However, CSE had no effect on TNF-α secretion and NF-κB activation. CSE induced an increase in intracellular Ca2+ concentration in 64% of HBSMCs. CSE reduced the contractile ability of HBSMCs, and the ability was enhanced by NAC treatment. These results demonstrate that CSE treatment induces cell death and reduces migration and contraction by increasing ROS generation in normal HBSMCs. These results suggest that CSE may induce airway change through cell death and reduction in migration and contraction of normal HBSMCs.

Follicular cystic ovary (FCO) is one of the most frequently diagnosed ovarian diseases and is a major cause of reproductive failure in mammalian species. However, the mechanism by which FCO is induced remains unclear. Genetic alterations which affect the functioning of many kinds of cells and/or tissues could be present in cystic ovaries. In this study, we performed a comparison analysis of gene expression in order to identify new molecules useful in discrimination of bovine FCO with follicular cystic follicles (FCFs). Normal follicles and FCFs were classified based on their sizes (5 to 10 mm and ≥25 mm). These follicles had granulosa cell layer and theca interna and the hormone 17β-estradiol (E2)/ progesterone (P4) ratio in follicles was greater than one. Perifollicular regions including follicles were used for the preparation of RNA or protein. Differentially expressed genes (DEG) that showed greater than a 2-fold change in expression were screened by the annealing control primer (ACP)-based PCR method using GeneFishing TM DEG kits in bovine normal follicles and FCFs. We identified two DEGs in the FCFs: ribosomal protein L15 (RPL15) and microtubule-associated protein 1B (MAP1B) based on BLAST searches of the NCBI GenBank. Consistent with the ACP analysis, semi-quantitative PCR data and Western blot analyses revealed an up-regulation of RPL15 and a down-regulation of MAP1B in FCFs. These results suggest that RPL15 and MAP1B may be involved in the regulation of pathological processes in bovine FCOs and may help to establish a bovine gene data-base for the discrimination of FCOs from normal ovaries.

The use of chemical techniques to study biological systems (often referred to currently as chemical biology) has become a powerful tool for both drug discovery and the development of novel diagnostic strategies. In tuberculosis, such tools have been applied to identifying drug targets from hit compounds, matching high-throughput screening hits against large numbers of isolated protein targets and identifying classes of enzymes with important functions. Metabolites unique to mycobacteria have provided important starting points for the development of innovative tools. For example, the unique biology of trehalose has provided both novel diagnostic strategies as well as probes of in vivo biological processes that are difficult to study any other way. Other mycobacterial metabolites are potentially valuable starting points and have the potential to illuminate new aspects of mycobacterial pathogenesis.

Numerous studies have suggested that K C channels regulate a wide range of physiological processes in mammalian cells. However, little is known about the specific function of K C channels in germ cells. In this study, mouse zygotes were cultured in a medium containing K C channel blockers to identify the functional role of K C channels in mouse embryonic development. Voltage-dependent K C channel blockers, such as tetraethylammonium and BaCl 2 , had no effect on embryonic development to the blastocyst stage, whereas K 2P channel blockers, such as quinine, selective serotonin reuptake inhibitors (fluoxetine, paroxetine, and citalopram), gadolinium trichloride, anandamide, ruthenium red, and zinc chloride, significantly decreased blastocyst formation (P!0.05). RT-PCR data showed that members of the K 2P channel family, specifically KCNK2, KCNK10, KCNK4, KCNK3, and KCNK9, were expressed in mouse oocytes and embryos. In addition, their mRNA expression levels, except Kcnk3, were up-regulated by above ninefold in morula-stage embryos compared with 2-cell stage embryos (2-cells). Immunocytochemical data showed that KCNK2, KCNK10, KCNK4, KCNK3, and KCNK9 channel proteins were expressed in the membrane of oocytes, 2-cells, and blastocysts. Each siRNA injection targeted at Kcnk2, Kcnk10, Kcnk4, Kcnk3, and Kcnk9 significantly decreased blastocyst formation by w38% compared with scrambled siRNA injection (P!0.05). The blockade of K 2P channels acidified the intracellular pH and depolarized the membrane potential. These results suggest that K 2P channels could improve mouse embryonic development through the modulation of gating by activators.