These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.

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.

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.

No abstract

We reported previously that the activity of the large-conductance calciumactivated potassium channels (BK Ca channel) could be strongly potentiated by certain derivatives of benzofuroindole scaffold when treated from extracellular side of the membrane (Gormemis et al., 2005; Ha et al., 2006). In order to localize the receptor site on the BK Ca channel, we surveyed the effects of CTBIC, the most potent benzofuroindole compound, on various K þ channels. While the compound increase the activity of voltage-gated K þ channels, K V 1.5 and HERG, CTBIC did not affect the activity of inward rectifier K þ channel, Kir3.1, significantly. Intriguingly enough, the same compound greatly decreased the activity of SK2, a different subclass of Ca 2þ -activated K þ channel. In addition, the affinity of charybdotoxin, a peptide pore-blocker, was reduced by the co-treatment with CTBIC, whereas that of tetraethylammonium, a small pore-blocking quaternary ammonium, was not altered. Guided by these results, we performed mutagenesis studies on the outer vestibule of the BK Ca channel to localize the residues that affect the binding of CTBIC. We identified three residues in the loop that connects with the pore-forming region of the channel, which was strongly affected by alanine substitution. Our results suggest that the turret region of the BK Ca channel may play a critical role in the modulation of the channel activity and may thus represent a therapeutic target site of K þ channels.