1 The aim of this work was to study the effects of N-salicyloyltryptamine (STP), a novel anticonvulsant agent, on voltage-gated ion channels in GH3 cells. 2 In this study, we show that STP at 17 mM inhibited up to 59.2710.4% of the I to and 73.178.56% of the I KD K þ currents in GH3 cells. Moreover, the inhibitory activity of the drug STP on K þ currents was dose-dependent (IC 50 ¼ 34.678.14 mM for I to ) and partially reversible after washing off. 3 Repeated stimulation at 1 Hz (STP at 17 mM) led to the total disappearance of I to current, and an enhancement of I KD . 4 In the cell-attached configuration, application of STP to the bath increased the open probability of large-conductance Ca 2 þ -activated K þ channels. 5 STP at 17 mM inhibited the L-type Ca 2 þ current by 54.977.50% without any significant changes in the voltage dependence. 6 STP at 170 mM inhibited the TTX-sensitive Na þ current by 22.172.41%. At a lower concentration (17 mM), no effect on I Na was observed. 7 The pharmacological profile described here might contribute to the neuroprotective effect exerted by this compound in experimental 'in vivo' models.

Background: Aging may be defined as gradual and progressive changes in an organism that increase the probability of death. Accumulating evidence now indicates that the sum of deleterious free radical reactions going on continuously throughout cells and tissues constitutes the aging process or is a major contributor to it. Objective: The aim of this paper was to study the correlation between NADPH oxidase and protein kinase C (PKC) in the reactive oxygen species (ROS) production related to age. Methods: The age-induced ROS generation was studied in healthy subjects ranging in age from 20 to 80 years, divided into six age groups: (1) 20–29, (2) 30–39, (3) 40–49, (4) 50–59, (5) 60–69, and (6) 70–80 years. The ROS were quantified using a chemiluminescence assay (luminol dependent) and the results expressed as RLU/s at maximum peak and total chemiluminescence (integral under the curve RLU/s). Results: Our results demonstrate a significant increase of the ROS production from 40 years of age (age groups 3–6). In the age groups 1 and 2, we did not observe a significant difference (p > 0.05). These data suggest an increase of the ROS production from 40 to 49 years of age which may be induced by the PKC activity. The selective PKC inhibitor (calphostin C) abrogated the stimulatory effect of phorbol-12,13-dibutyrate on the ROS production. However, the NADPH oxidase inhibitor diphenylene iodonium did not inhibit the total ROS production by granulocytes in relation to age. Conclusions: These data suggest a correlation between age-related PKC activity, NADPH oxidase phosphorylation, and ROS production. The above correlations between unspecific and inflammatory responses related to age are discussed.

Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness. To explain this relationship, different theories, associated with pH changes, gene expression and intracellular Ca2+, have been proposed in an attempt to better understand the role of these ion channels in breast cancer. However, these theories are having difficulty being accepted because most of the findings are contrary to the present scientific knowledge. Several studies have shown that VGSC are related to different types of cancer, making them a promising pharmacological target against this debilitating disease. Molecular biology and cell electrophysiology have been used to look for new forms of treatment aiming to reduce aggressiveness and the disease progress.

T-type Ca 2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca 2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 ± 1.87 ms (N = 16). The I-V relationship measured with Ca 2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 ± 2.4 and 6.7 ± 0.3 mV (prepulse of -120 mV, N = 15), and -27.0 ± 0.97 and 7.5 ± 0.7 mV (prepulse of -40 mV, N = 9). The 8-mV shift in the activation mid-point was statistically significant (P < 0.05). The tail currents decayed biexponentially suggesting two different T-type Ca 2+ channel populations. RT-PCR revealed the presence of α1G (CaV3.1) and α1I (CaV3.3) T-type Ca 2+ channel mRNA transcripts. Correspondence

We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca current density and this phenomenon impacts proliferation rate in GH3 cells.

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SUMMARY Cancer is characterized by the disordered growth of cells that have high capacity of invasion to the tissues and organs. One of the types of tumour that has national incidence and high mortality is breast cancer. Studies show that in addition to hereditary factors, lifestyle and environmental factors, there are factors related to emotional distress (mourning), which interfere with the development of breast cancer. Thus, it is necessary to investigate if the experience of mourning can trigger the appearance of the tumour. For this, an integrative review was performed to verify the existence of the relationship between mourning and development of breast cancer, which presented contradictory results. Methodological errors and lack of access to important information, such as alcohol and tobacco use, were pointed out as the main causes of the contradiction found. A possible mechanism involving cortisol release has been proposed, but more research is needed to make it clear whether the association between mourning and breast cancer really exists, and by what path.

Breast cancer is the most prevalent cancer in women worldwide. Its molecular subtypes are based on the presence/absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). MACL-1 and MGSO-3 are cell lines derived from primary tumor sites of patients diagnosed with luminal A subtype carcinoma (ER+/PR+/HER2−) and ductal carcinoma in situ (ER−/PR−/HER2+), respectively. However, these cell lines lost the expression of these markers over cell culturing, and both have triple-negative phenotypes (ER−/PR−/HER2−), which has the poorest prognosis. Here, we sought to study the proteome signature of MGSO-3 and MACL-1, comparing them with the epithelial cell line MCF-10A and the well-established metastatic-derived breast cancer cell line MDA-MB-231. Our results showed that proteins associated with the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) were upregulated in MGSO-3 and MACL-1 cells. These cell lines also showed upregulation of pro-apoptotic proteins when compared with MDA-MB-231. The molecular differences highlighted in this study may clarify the molecular basis behind cancer cells functioning and may reveal novel signatures across the breast cancer cell models.