Role of Filamin A in Growth and Migration of Breast Cancer-Review.

Despite ongoing research in the field of breast cancer, the morbidity rates indicate that the disease remains a significant challenge. While patients with primary tumors have relatively high survival rates, these chances significantly decrease once metastasis begins. Thus, exploring alternative approaches, such as targeting proteins overexpressed in malignancies, remains significant. Filamin A (FLNa), an actin-binding protein (ABP), is involved in various cellular processes, including cell migration, adhesion, proliferation, and DNA repair. Overexpression of the protein was confirmed in samples from patients with numerous oncological diseases such as prostate, lung, gastric, colorectal, and pancreatic cancer, as well as breast cancer. Although most researchers concur on its role in promoting breast cancer progression and aggressiveness, discrepancies exist among studies. Moreover, the precise mechanisms through which FLNa affects cell migration, invasion, and even cancer progression remain unclear, highlighting the need for further research. To evaluate FLNa's potential as a therapeutic target, we have summarized its roles in breast cancer.

Fascin in migration and metastasis of breast cancer cells - A review.

Cancer cell migration and metastasis are the biggest problems in the treatment of cancer patients. The most aggressive breast cancer (BC) is the triple-negative type. Therefore, effective therapeutic targets that limit cell migration are sought. One such target may be fascin, as its overexpression is characteristic to triple-negative breast cancer. The high level of fascin enables the formation of protrusion and thus promotes the invasion of cancer cells. Fascin also shows co-localization or functional relationships with other proteins. These are proteins involved in the epithelial-mesenchymal transition process, vimentin, cadherins, ß-catenin, and matrix metalloproteinases 2/9 (MMP-2/9). Fascin is also involved in many signaling pathways protein kinase C-δ (PKCδ), Wnt/ß-catenin, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and phosphatidylinositol 3-kinase (PI3K)-Akt. Therefore, in this article, we review currently available in vitro studies and compare them with The Cancer Genome Atlas (TCGA) data analysis of BC patients to demonstrate the role of fascin in the migration and invasion of cancer cells.

Synergistic effect of metformin and doxorubicin on the metastatic potential of T24 cells.

BACKGROUND: The motor ability of cancer cells to cross the basement membrane contributes to their implantation in a new location. Metastasis is a significant factor that worsens the prognosis of cancer patients. Thus, reducing cell invasiveness is an important aspect of anticancer therapy, also in bladder cancer treatment. MATERIAL: The study material was the T24 cell line of human urinary bladder cancer. The migratory potential of the cells and the effect of the treatment with individually doses and synergistic combination of doxorubicin and metformin in the 500:1 ratio for 24 h were analyzed. RESULTS: The results obtained show a compound-initiated decrease in the motor abilities of bladder cancer cells compared to controls. A decrease in the rate of colony formation was observed, as well as inhibition of migration through inserts. The visualized reorganization of the vimentin and actin networks confirms the drug-initiated limitation of the metastatic potential of T24 cells. CONCLUSION: According to our knowledge, we are the first to show, that combination of doxorubicin and metformin also worth considering in the treatment of bladder cancer. We showed that simultaneous administration of these cytostatic enhances the antiproliferative effect of drugs, but also limits cells' migratory potential.

Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines.

Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).

Downregulation of FHOD1 Inhibits Metastatic Potential in A549 Cells.

PURPOSE: Metastasis remains a serious clinical problem in which epithelial-to-mesenchymal transition is strictly involved. The change of cell phenotype is closely related to the dynamics of the cytoskeleton. Regarding the great interest in microfilaments, the manipulation of ABPs (actin-binding proteins) appears to be an interesting treatment strategy. MATERIAL: The research material was the highly aggressive A549 cells with FHOD1 (F FH1/FH2 domain-containing protein 1) downregulation. The metastatic potential of the cells and the sensitivity to treatment with alkaloids (piperlongumine, sanguinarine) were analyzed. RESULTS: In comparison to A549 cells with naïve expression of FHOD1, those after manipulation were characterized by a reduced migratory potential. The obtained results were associated with microfilaments and vimentin reorganization induced by the manipulation of FHOD1 together with alkaloids treatment. The result was also an increase in the percentage of late apoptotic cells. CONCLUSION: Downregulation of FHOD1 induced reorganization of microfilament network followed by the reduction in the metastatic potential of the A549 cells, as well as their sensitization to selected compounds. The presented results and the analysis of clinical data indicate the possibility of transferring research from the basic level to in vivo models in the context of manipulation of ABPs as a new therapeutic target in oncology.

Cyclin F Downregulation Affects Epithelial-Mesenchymal Transition Increasing Proliferation and Migration of the A-375 Melanoma Cell Line.

BACKGROUND: Cyclins are well-known cell cycle regulators. The activation of cyclin-dependent kinases by cyclins allows orchestration of the complicated cell cycle machinery and drives the cell from the G1 phase to the end of the mitotic phase. In recent years, it has become evident that cyclins are involved in processes beyond the cell cycle. Cyclin F does not activate CDKs but forms part of the Skp1-Cul1-F-box (SCF) complex where it is responsible for protein target recognition and subsequent degradation in a proteasome-dependent manner. RESULTS: Here, we report that the downregulation of cyclin F in the A-375 melanoma cell line increases cell viability and colony formation in a cell cycle independent manner. Lower levels of cyclin F do not appear to affect the cell cycle, based on flow cytometry measuring BrdU incorporation and propidium iodide staining. By means of immunofluorescence staining and Western blot analysis, we observed changes in cell morphology-related markers which suggested ongoing epithelial-mesenchymal transition (EMT) in response to cyclin F downregulation. Increases in vimentin and N-cadherin protein levels, decreases in levels of epithelial markers such as ZO-1, along with changes in morphology to a spindle-like shape with the appearance of actin stress fibers, are all hallmarks of EMT. These changes are associated with increased invasive and migratory potential, based on 2D migration assays. Moreover, we observe an increase in RhoABC, talin and paxillin levels, the proteins involved in controlling cell signaling and motility. Lastly, upon knocking down cyclin F expression, we observed a decrease in thrombospondin-1 expression, suggesting a role of cyclin F in angiogenesis. CONCLUSION: Cyclin F depletion induces proliferation and EMT processes in the A-375 melanoma model.

The effect of low doses of doxorubicin on the rat glioma C6 cells in the context of the proteins involved in intercellular interactions.

The aim of this investigation was to determine the effect of doxorubicin on F-actin rearrangement and ß-catenin and cofilin-1 in a rat glioma C6 cell line in combination with changes in their morphology and ultrastructure. The experimental material constituted rat glioma C6 cell line. The cells were incubated with sublethal doses of doxorubicin in the concentration of 50, 100 and 200 nM. The blue trypan dye method was used to determine the number of dead cells. Morphological and ultrastructural changes in the cells were evaluated using light and transmission electron microscope, respectively. In order to determine the rearrangements and level of expression of F-actin, ß-catenin and cofilin-1 they were analyzed using a fluorecence microscope. In turn, cell death and cell cycle were evaluated by Guava 6HT-2 L Cytometer. The performed experiments showed a dose-dependent decrease in the survival of C6 cells after treatment with doxorubicin. The analysis of cell death showed a dose-dependent increase in the population of apoptotic and necrotic cells. These results were confirmed by microscopy observation. The changes in morphology, ultrastructure, and rearrangements of F-actin, ß-catenin and cofilin-1 were also observed. The results obtained in the study showed that sublethal concentrations of doxorubicin influenced the structure of F-actin and other proteins involved in cell-cell interactions. Moreover, mitotic catastrophe may preceding apoptosis, what suggest the cytotoxic effect of low dose of doxorubicin. Furthermore, our results confirmed the multi-dimensional mechanism of DOX action in tumor cells.

Involvement of Actin and Actin-Binding Proteins in Carcinogenesis.

The actin cytoskeleton plays a crucial role in many cellular processes while its reorganization is important in maintaining cell homeostasis. However, in the case of cancer cells, actin and ABPs (actin-binding proteins) are involved in all stages of carcinogenesis. Literature has reported that ABPs such as SATB1 (special AT-rich binding protein 1), WASP (Wiskott-Aldrich syndrome protein), nesprin, and villin take part in the initial step of carcinogenesis by regulating oncogene expression. Additionally, changes in actin localization promote cell proliferation by inhibiting apoptosis (SATB1). In turn, migration and invasion of cancer cells are based on the formation of actin-rich protrusions (Arp2/3 complex, filamin A, fascin, α-actinin, and cofilin). Importantly, more and more scientists suggest that microfilaments together with the associated proteins mediate tumor vascularization. Hence, the presented article aims to summarize literature reports in the context of the potential role of actin and ABPs in all steps of carcinogenesis.

Analysis of serum homocysteine in the laboratory practice - comparison of the direct chemiluminescence immunoassay and high performance liquid chromatography coupled with fluorescent detection.

INTRODUCTION: Effective diagnosis of cardiovascular diseases requires the right tools to be used enabling selective and sensitive analysis of their biomarkers. One of them is homocysteine (Hcy), nowadays determined by immunoassays and chromatographic methods. This study aims to compare the results obtained by direct chemiluminescence immunoassay (CLIA) and high performance liquid chromatography with fluorescent detection (HPLC-FD) using commercial kits. MATERIALS AND METHODS: Homocysteine concentration was determined in serum samples obtained from 101 individuals, using Atellica IM HCY (Siemens Healthineers, Erlangen, Germany) and HCY in plasma/serum - HPLC-FD (Chromsystems Instruments & Chemicals GmbH, Gräfelfing, Germany) tests validated for routine analysis. The latter was applied as a reference method. The comparability and agreement between the tested methods were evaluated using the Passing-Bablok (PB) regression analysis and the Bland-Altman (BA) method of the differences analysis. RESULTS: Studies showed that CLIA gives higher Hcy concentrations (15.7 ± 4.14 µmol/L). Passing-Bablok regression analysis of the results obtained with CLIA (y) compared with HPLC-FD (x) yielded an intercept of 0.22 (95%CI: - 2.16 to 2.46) and slope of 1.58 (95%CI: 1.33 to 1.87). Bland-Altman analysis demonstrated a systematic positive bias for CLIA of 5.85 ± 2.77 µmol/L. CONCLUSIONS: Methods disagreement precludes their interchangeability. Lower Hcy values by HPLC-FD result from its greater selectivity. High performance liquid chromatography with fluorescent detection should be considered as preferential method for analysing Hcy in blood serum as well as the recommended reference method for routine clinical analysis. This fact, however, imposes the need to establish new reference ranges.

The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer.

BACKGROUND: Cancers are one of the leading causes of deaths nowadays. The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine. Therefore, the evaluation of the influence of two alkaloids-piperlongumine (PL), sanguinarine (SAN) and their combination-on the basic life processes of the A549 cell line was considered reasonable. METHODS: The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death, changes in the distribution of cell cycle phases, reorganization of cytoskeleton and metastatic potential of A549 cells. The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines: MCF-7, H1299 and HepG2. RESULTS: The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells. Additionally, the compounds and their combination did not exhibit a cytotoxic effect against normal cells. The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition. CONCLUSION: Selected alkaloids exhibit a cytotoxic effect on A549 cells. In turn, treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species (ROS).

Involvement of Actin in Autophagy and Autophagy-Dependent Multidrug Resistance in Cancer.

Currently, autophagy in the context of cancer progression arouses a lot of controversy. It is connected with the possibility of switching the nature of this process from cytotoxic to cytoprotective and vice versa depending on the treatment. At the same time, autophagy of cytoprotective character may be one of the factors determining multidrug resistance, as intensification of the process is observed in patients with poorer prognosis. The exact mechanism of this relationship is not yet fully understood; however, it is suggested that one of the elements of the puzzle may be a cytoskeleton. In the latest literature reports, more and more attention is paid to the involvement of actin in the autophagy. The role of this protein is linked to the formation of autophagosomes, which are necessary element of the process. However, based on the proven effectiveness of manipulation of the actin pool, it seems to be an attractive alternative in breaking autophagy-dependent multidrug resistance in cancer.

Edaravone presents antidepressant-like activity in corticosterone model of depression in mice with possible role of Fkbp5, Comt, Adora1 and Slc6a15 genes.

Chronic exposure to environmental-like stress leads to dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and to appearance of oxidative stress, which is implicated in the development of depression-like behaviour. Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) exhibits a neuroprotective effect attributed to the potent free radical scavenging. This study was designed to assess antidepressant-like activity of edaravone based on behavioural tests in the animal model of depression. Furthermore, to elucidate its mechanisms, the expression of Fkbp5, Comt, Adora and Slc6a15 genes involved in turnover of neurotransmitters was analysed. In order to evaluate the antioxidant features of edaravone, DNA's oxidative damage was determined. The mice were injected subcutaneously (sc) with 40 mg/kg corticosterone, chronically for 21 days. Paroxetine (10 mg/kg) (a selective serotonin reuptake inhibitor) and edaravone (10 mg/kg) were administered separately (ip) 30 min prior to the corticosterone injection. After 21-days of treatment with respective drugs, the mice were decapitated and the prefrontal cortex was rapidly dissected and used for determination of DNA's oxidative damage and the real-time PCR analysis. Edaravone ameliorated behavioural impairments in sucrose preference test (SPT) and forced swim test (FST). A possible role in Fkbp5, Comt, Adora1 and Slc6a15 genes' expression in mediating this effect is postulated. Both edaravone and paroxetine have no effect on corticosterone-induced DNA's oxidative damage.

The cytotoxic effect of oxymatrine on basic cellular processes of A549 non-small lung cancer cells.

Oxymatrine is the alkaloid derived from the root of Sophora species. This compound is proven to exhibit anti-viral, anti-asthmatic, anti-fibrotic and anti-inflammatory properties. Additionally, oxymatrine is able to promote cancer cells apoptosis and inhibit their proliferation. The aim of this study was to present the influence of oxymatrine on non-small cell lung cancer cells. The results indicate, that this agent induces dose-dependent cell death mainly through ER stress-induced apoptosis pathway. We also suggest that the oxymatrine reduces the metastatic potential by inhibition of the EMT process, as A549 cells treated with chosen doses of the compound were characterized by a decrease in the expression of the N-cadherin, vimentin and the elevation of E-cadherin level. Moreover, the study broadens the knowledge on so far poorly understood aspect of the influence of oxymatrine on the cytoskeleton structure.

Altered expression of genes involved in brain energy metabolism as adaptive responses in rats exposed to chronic variable stress; changes in cortical level of glucogenic and neuroactive amino acids.

Brain metabolism is closely associated with neuronal activity and enables the accurate synthesis and function of neurotransmitters. Although previous studies have demonstrated that chronic stress is associated with the overproduction of reactive oxygen species (ROS), which leads to oxidative stress and the disruption of glucose metabolism, the molecular mechanisms and cerebral gluconeogenesis in depression have not yet been completely elucidated. In order to examine this subject, the present study evaluated changes in the expression of selected genes involved in the glycolytic pathway and the levels of glucogenic and neuroactive amino acids in the brain of rats exposed to chronic variable stress. Male Wistar rats (50­55 days old, weighing 200­250 g) were divided into two groups: control and stressed, and the rats in the stressed group were exposed to stress conditions for 40 days. Depressive­like states were observed and recorded by measuring the body weight and forced swim test (FST). The mRNA levels of Slc2a3 (coding GLUT3) and Tfam (activator of mitochondrial transcription and a participant in mitochondrial genome replication) were markedly increased, while a decrease in the expression of Ldhb and GAPDH was also observed. These modifications were associated with the redirection of glucose metabolism to appropriate defensive pathways under chronic stress conditions, and an increased ability to maintain mitochondrial function as potential adaptive responses. A marked reduction of glucogenic and neuroactive amino acids levels indicate the support of energy metabolism by stimulation of the gluconeogenesis pathway. The findings of the present study provide a novel insight into the molecular and biochemical events that impact the development of depression under chronic stress conditions, and they may identify novel targets for therapeutic intervention.

Novel 2,3­disubstituted 1,3­thiazolidin­4­one derivatives as potential antitumor agents in renal cell adenocarcinoma.

Cancer represents one of the main causes of mortality in developed countries. In particular, the overall survival of patients with renal cell carcinoma (RCC) remains poor and the available cytostatic agents are insufficient. Therefore, there is an urgent requirement to identify more effective and safer anticancer drugs. Recently, the evaluation of antitumor activity appeared to be promising for thiazolidinone derivatives. The present study presents the synthesis and the cytotoxicity assays of 1,3­thiazolidin­4­ones. The newly synthesized substances were screened in vitro against selected cancer human renal cell adenocarcinoma cells (769­P), human hepatoblastoma­derived cells (HepG2) and normal green monkey kidney cells (GMK) as a reference cell line. N­[2­(4­methylphenyl)­4­oxo­1,3­thiazolidin­3­yl]acetamide and N­[2­(4­methylphenyl)­4­oxo­1,3­thiazolidin­3­yl]benzamide displayed significant antiproliferative activity towards 769­P. To elucidate the mechanisms of the cytotoxic actions, additional studies on the cell cycle and apoptosis were performed. The aforementioned compounds were responsible for G1 cell cycle arrest and the decrease in cell distribution in the G2 phase in a dose­dependent manner, which prevents mitotic divisions of the 769­P cells. In addition, these novel 2,3­disubstituted 1,3­thiazolidin­4­ones slightly induced apoptosis in 769­P in a dose­dependent manner. It was hypothesized that the 4­methylphenyl group at position 2 of the thiazolidin­4­one scaffold may be regarded as a promising moiety for further development of this group of compounds. Therefore, benzamide moiety appeared to be crucial for triggering cells to apoptotic cell death.

Lidocaine induces protective autophagy in rat C6 glioma cell line.

Malignant glioma is the most common type of brain cancer with poor prognosis. Surgical resection, chemotherapy and radiotherapy are the main therapeutic options; however, in addition to their insufficient efficacy, they are associated with the pain experienced by patients. To relieve pain, local anesthetics, such as lidocaine can be used. In the present study, the effects of lidocaine on the C6 rat glioma cell line were investigated. An MTT assay and Annexin V/propidium iodide analysis indicated the increase in the percentage of apoptotic and necrotic cells in response to lidocaine. Furthermore, light microscopy analysis on the ultrastructural level presented the occurrence of vacuole­like structures associated with autophagy, which was supported by the analysis of autophagy markers (microtubule­associated protein 1A/1B­light chain 3, acridine orange and Beclin­1). Additionally, reorganization of the cytoskeleton was observed following treatment with lidocaine, which serves an important role in the course of autophagy. To determine the nature of autophagy, an inhibitor, bafilomycin A1 was applied. This compound suppressed the fusion of autophagosomes with lysosomes and increased the percentage of apoptotic cells. These results demonstrated that lidocaine may induce cytoprotective autophagy and that manipulation of this process could be an alternative therapeutic strategy in the treatment of cancer.

Resveratrol Limits Lipogenesis and Enhance Mitochondrial Activity in HepG2 Cells.

PURPOSE: The aim of this study was to evaluate the effect of resveratrol on de novo lipogenesis in HepG2 cells caused by high glucose concentrations. Increased lipogenesis in the liver is the main reason for the development of nonalcoholic fatty liver disease (NAFLD) - currently one of the most common chronic liver diseases. In developed countries, this disease is mostly associated with nutritional disorders, resulting from the increasing consumption of monosaccharides. Resveratrol is a natural polyphenol with a promising potential for NAFLD treatment. METHODS: The steatosis of HepG2 cells was visualized using the intracellular lipid staining by Nile Red dye with a fluorescence microscope. This study also evaluated the effect of resveratrol on the mitochondrial activity (MitoTracker Green staining), dsDNA (Hoechst 33342 staining) and the viability of HepG2 cells treated with high glucose concentrations (25 and 33 mM). RESULTS: Current study showed that high glucose concentrations induced fat-overloading in HepG2 cells (microvacuolar steatosis occurred in most of the cells). Resveratrol (20 µM) limits the steatosis induction in HepG2 cells by glucose and increased the mitochondrial activity of cells. Resveratrol did not affect the viability of HepG2 cells. CONCLUSION: This beneficial effect could be helpful in the treatment of NAFLD.

α-Tocopherol Ameliorates Redox Equilibrium and Reduces Inflammatory Response Caused by Chronic Variable Stress.

Chronic exposure to stress factors contributes to the development of depression by generating excess of reactive oxygen species which leads to oxidative stress and inflammatory processes. The aim of the study was to assess the potential protective properties of α-tocopherol supplementation on the rats exposed to chronic variable stress (CVS). Male Wistar rats (50-55 days old, weighing 200-250 g) were divided into three groups (n=10): control, stressed, and stressed and receiving (+)-α-tocopherol solution in a dose of 100 mg/kg/day. Rats in the stressed groups were exposed to CVS for 40 days. Markers of redox disorders (glutathione reduced and oxidized levels, GSH/GSSG ratio, glutathione peroxidase, glutathione reductase activities, total antioxidant status, and lipid peroxidation) and inflammatory response (IL-1ß, IL6, and TNF-α) were determined in the blood. Additionally, molecular biomarkers of depression (expression of Fkbp5 and Tph2) were studied in hippocampus. The biochemical analysis was inconclusive about the presence of oxidative stress in the blood of rats exposed to CVS. However, changes in all parameters suggest presence of redox equilibrium disorders. Similarly, activation of inflammatory processes was observed as a result of CVS. Molecular effects of environmental stress in hippocampus were also observed. Generally, α-tocopherol ameliorated redox equilibrium disorders, tempered inflammatory response, and protected from changes in determined molecular markers of depression.

The effect of piperlongumine on endothelial and lung adenocarcinoma cells with regulated expression of profilin-1.

PURPOSE: The aim of the study was to evaluate the effect of piperlongumine (2 and 4 µM) on endothelial EA.hy926 and lung adenocarcinoma A549 cells with regulated expression of profilin-1 (PFN1). MATERIAL AND METHODS: The cytotoxicity of alkaloid was evaluated by MTT assay, while cell death was assessed using double staining with annexin V and propidium iodide. Subsequently, the level of PFN1 1) upregulation in EA.hy926 endothelial cells and 2) downregulation in A549 lung adenocarcinoma cells. The next step was the analysis of the effect of PFN1 manipulation on cytoskeletal proteins. RESULTS: The results showed that piperlongumine may inhibit proliferation of EA.hy926 and A549 cell lines and also induce cell death in a dose-dependent manner. Furthermore, endothelial cells with PFN1 overexpression showed lower sensitivity to alkaloid and strengthening of cell-cell interactions. In the case of A549 cells, loss of PFN1 expression resulted in a lower percentage of early apoptotic cells, reorganization of F-actin and vimentin network, and reduction of migratory potential. CONCLUSION: We suggest that upregulation of PFN1 in endothelial cell line may stabilize the cell junctions. In turn, PFN1 downregulation in A549 cells probably suppresses cell migration and sensitizes cells to anticancer agents.

8-Cyclopentyl-1,3-dimethylxanthine enhances effectiveness of antidepressant in behavioral tests and modulates redox balance in the cerebral cortex of mice.

The objective of our study was to investigate whether 8-cyclopentyl-1,3-dimethylxanthine (CPT), associated with the adenosine system, enhances the antidepressant efficacy of antidepressant. All experiments were carried out on Albino Swiss mice. Following drugs: CPT (3 mg/kg) and imipramine (15 mg/kg) were administered intraperitoneally (ip), 60 min before tests. Two behavioral tests on antidepressant capability - a forced swim test (FST) and a tail suspension test (TST) - were performed. To examine whether co-administration of CPT with antidepressants affects the redox balance, the lipid peroxidation products (LPO), glutathione (GSH), glutathione disulfide (GSSG), nicotinamide adenine dinucleotide phosphate (NADP+), and reduced nicotinamide adenine dinucleotide phosphate (NADPH) were determined in the cerebral cortex. The results have demonstrated a CPT-induced enhancement of the antidepressant-like effect of imipramine both in the FST and TST, which may indicate that the adenosine system may be involved in the increasing the effect of antidepressant. Co-administration of CPT with imipramine, such as imipramine alone, decreased the NADP+ and LPO concentrations and increased the GSH/GSSG ratio in comparison to the control, which may confirm beneficial - but comparable to imipramine - effect on redox balance under environmental stress conditions. An increase in the concentration of GSSG in the cortex of animals treated with imipramine in ineffective dose compared to control and no such changes after combined administration of both drugs may suggest a favorable oxidation-reduction potential resulting from their synergistic antidepressant effect.