No abstract available.
Carcinoma, Squamous Cell* ; Cell Line* ; Suramin*

Experimental study was done to investigate the effect of suramin on the in vitro and in vivo proliferation and metastasis of penile squamous carcinoma cell line(CUPE-1), morphological changes of CUPE-1 cells induced by suramin and mechanism of action of suramin. Suramin inhibited in vitro proliferation of CUPE-1 significantly with 1C50 of 100 microgram/ml media. In vitro antiproliferative effect of suramin on CUPE-1 was reversible after stopping administration of the drug. Weekly intraperitoneal administration of 200 mg/kg of suramin to nude mouse inhibited the proliferation and metastasis of intraperitoneally implanted CUPE-1 cells significantly. but did not show significant effect on the proliferation of subcutaneously implanted CUPE-1 cells. Suramin induced senile changes on ultrastructure of CUPE-1 cells. Suramin of 300 microgram/ml inhibited the prolireration-stimulating effect of EGF significantly, whereas, suramin of 100 microgram/ml did not inhibit the effect of EGF significantly. Suramin did not show significant cytotoxicity on 3H-thymidine release assay. These results suggest that suramin is a promising drug for the treatment of advanced penile squamous cell carcinoma and blood level of suramin in clinical trial should be continuously maintained in about 300 microgram/ml, and that the main machanism of suramin against CUPE-1 is cytostatic. by antagonizing the action of EGF and inducing growth arrest and senile change.
Animals ; Carcinoma, Squamous Cell* ; Epidermal Growth Factor ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Robenidine ; Suramin

To clarify the effect of extracellular ATP in cultured C6 glioma cells, ATP-induced cytosolic free calcium ((Ca2+)i) mobilization and cell proliferation were investigated. ATP-induced (Ca2+)i increased in a dose-dependent manner (10-7 M apprx 10-3 M). ATP-induced (Ca2+)i increases were slightly slowed in extracellular calcium-free conditions especially in sustained phase. ATP-induced (Ca2+)i increment was also inhibited by the pretreatment of U73122, a phospholipase C (PLC) inhibitor, in a time-dependent manner. Suramin, a putative P2Y receptor antagonist, dose-dependently weakened ATP-induced (Ca2+)i mobilization. Significant increases in cell proliferation were observed at 2, 3, and 4 days after ATP was added. Stimulated cell proliferation was also observed with adenosine at days 2 and 3. This cell proliferation was significantly inhibited by the treatment with suramin. Ionomycin also stimulated cell proliferation in a concentration-dependent manner. In conclusion, we suggest that extracellular ATP stimulates C6 glioma cell proliferation via intracellular free calcium mobilization mediated by purinoceptor.
Adenosine ; Adenosine Triphosphate* ; Calcium* ; Cell Proliferation* ; Cytosol ; Glioma* ; Ionomycin ; Receptors, Purinergic ; Suramin ; Type C Phospholipases

Autism spectrum disorder is a rapidly increasing heterogeneous neurodevelopmental syndrome, remarked by persistent deficit in social communication, and restricted, repetitive patterns of behavior and interest. Lately, maternal immune activation and micgroglial dysfunction in the developing brain have been gaining mounting evidence and leading to studies of various novel agents as potential treatment options. A few immunomodulatory treatment options—luteolin, minocycline, suramin, vitamin D, gut microbiota—are discussed in the current article, regarding the current understanding of their mechanisms and evidence for potential clinical use. More studies are warranted to understand their exact mechanisms of action and to verify efficacy and safety in human subjects.
Autism Spectrum Disorder* ; Autistic Disorder* ; Brain ; Humans ; Immunomodulation ; Microglia* ; Minocycline ; Suramin ; Vitamin D

Recently much interest has been expressed for the use of biological response modifiers and growth factor antagonists in the treatment or radiation and chemotherapeutic drug-refractory renal cell carcinoma. Herein antiproliferative effects of Suramin, human recombinanl tumor necrosis factor alpha (TNF-alpha) and human recombinant interferon alpha (IFN-alpha) as a single and in combination were studied in vito on human renal carcinoma cell line (Caki-1). Antiproliferative effect was evaluated by trypan blue dye exclusion assay after 3 days exposure to Suramin at 10, 30, 100, 300, 1,000 mcg/ ml. TNF-alpha at 1, 10, 50, 100, 500, 1,000 units/ml and IFN-alpha at 10, 100, 1,000. 10,000 units/ml concentration, respectively. In addition, effects of combined administration in tolerable peak plasma level or suramin (300 mcg/ml). TNF-alpha (500 units/ml) and IFN-alpha (1000 units/ml) were comparatively analyzed to those of single drug administration. The results were as follows: 1. Significant dose dependent antiproliferative effects were shown by Suramin at above 100 mcg/ml. TNF-alpha at above 500 units/ml and IFN-alpha at above 10 units/ml, respectively (p<0.05). 2. At peak plasma level, suramin, TNF-alpha and IFN-alpha showed less than 50% inhibition of proliferation. 3. On combined administration, suramin plus TNF-alpha (61.0%), Suramin plus IFN-alpha(71.7%) and TNF-alpha plus IFN-alpha (57.2%) induced significantly greater inhibition of proliferation (p<0.005). These results suggest that further in vivo study using combination of Suramin plus TNF-alpha Suramin plus IFN-alpha and TNF-alpha plus IFN-alpha is necessary and that these combination trials may become one of the treatment options for renal cell carcinoma.
Carcinoma, Renal Cell ; Cell Line* ; Humans* ; Immunologic Factors ; Interferon-alpha ; Necrosis* ; Plasma ; Suramin* ; Trypan Blue ; Tumor Necrosis Factor-alpha

OBJECTIVETo test the different contrctile responses of extracellular nucleotides, such as ATP, UTP and nucleotide uridine adenosine tetraphosphate (Up4A) in gastric longitudinal muscle (LM) and circular muscle (CM). Examined the effect of P2X and P2Y receptor antagonists (in this study, we used IP5I and suramin) and cyclooxygenase inhibitor (indomethacin) on Up4A induced contractile responses in LM and CM.

METHODSThe rats were sacrificed and the stomachs were opened to gain LM and CM. Using organ bath system to assess contrctile responses of smooth muscle.

RESULTSUp4A could induce contractile responses in both CM and LM, which were similar with ATP and UTP. IP5 did not attenuate Up4A could induce contractions in both LM and CM, but suramin and indomethacin significantly inhibited Up4A contraction in CM, but not in LM.

CONCLUSIONOur results suggest that extracellular nucleosides and their inhibitors induce different responses between LM and CM.

Adenosine Triphosphate ; pharmacology ; Animals ; Dinucleoside Phosphates ; pharmacology ; Indomethacin ; Muscle Contraction ; Muscle, Smooth ; physiology ; Nucleotides ; pharmacology ; Rats ; Suramin ; Uridine Triphosphate ; pharmacology

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation but the mechanism remains elusive. Red blood cells (RBCs) are known to augment HPV and to release more ATP as oxygen content falls. Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. Hence we hypothesized that ATP and leukotrienes are mediators of HPV produced during acute alveolar hypoxia. METHODS: In forty Sprague-Dawley rats, lungs were isolated and perfused. We administered ATP (10 micrometer) to the ATP group (n = 8), the ATP antagonist, suramin (100 micrometer) to the suramin group (n = 8), leukotriene C4 (LTC4, 5 microgram) to the LTC4 group (n = 8), the LTC4 antagonist, LY171883 (20 micrometer) to the LY171883 group (n = 8), and LTC4 (5 microgram) + ATP (10 micrometer) to the LTC4 + ATP group (n = 8) during normoxic ventilation. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. Baseline pulmonary artery pressure change after exposure to each drug and hypoxic pressor response between a period 21% normoxic gas ventilation and that of 3% hypoxic gas ventilation were measured. RESULTS: ATP and LTC4 + ATP increased baseline pulmonary artery pressures but LTC4 did not alter it. ATP did not affect hypoxic pressor response. Suramin, LY171883 and LTC4 + ATP inhibited the pressor response to hypoxia. LTC4 increased hypoxic pressor response. CONCLUSIONS: In isolated rat lungs, HPV may be mediated by ATP and LTC4 appears more likely to be a modulator than a mediator of HPV.
Acetophenones ; Adenosine Triphosphate ; Animals ; Anoxia ; Erythrocytes ; Leukotriene C4 ; Leukotrienes ; Lung ; Muscle, Smooth ; Oxygen ; Pulmonary Artery ; Pulmonary Circulation ; Rats ; Rats, Sprague-Dawley ; Suramin ; Tetrazoles ; Vasoconstriction ; Ventilation

Reactive oxygen species (ROS) and nitrogen species (RNS) are implicated in cellular signaling processes and as a cause of oxidative stress. Recent studies indicate that ROS and RNS are important signaling molecules involved in nociceptive transmission. Xanthine oxidase (XO) system is a well-known system for superoxide anions (O2(.-)) generation, and sodium nitroprusside (SNP) is a representative nitric oxide (NO) donor. Patch clamp recording in spinal slices was used to investigate the role of O2(.-) and NO on substantia gelatinosa (SG) neuronal excitability. Application of xanthine and xanthine oxidase (X/XO) compound induced membrane depolarization. Low concentration SNP (10 microM) induced depolarization of the membrane, whereas high concentration SNP (1 mM) evoked membrane hyperpolarization. These responses were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger). Addition of thapsigargin to an external calcium free solution for blocking synaptic transmission, led to significantly decreased X/XO-induced responses. Additionally, X/XO and SNP-induced responses were unchanged in the presence of intracellular applied PBN, indicative of the involvement of presynaptic action. Inclusion of GDP-beta-S or suramin (G protein inhibitors) in the patch pipette decreased SNP-induced responses, whereas it failed to decrease X/XO-induced responses. Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) decreased the effects of SNP, suggesting that these responses were mediated by direct oxidation of channel protein, whereas X/XO-induced responses were unchanged. These data suggested that ROS and RNS play distinct roles in the regulation of the membrane excitability of SG neurons related to the pain transmission.
Animals ; Calcium ; Ethylmaleimide ; Humans ; Membranes ; Neurons* ; Nitric Oxide ; Nitrogen* ; Nitroprusside ; Oxidative Stress ; Rats* ; Reactive Oxygen Species* ; Substantia Gelatinosa* ; Superoxides ; Suramin ; Synaptic Transmission ; Thapsigargin ; Tissue Donors ; Xanthine ; Xanthine Oxidase

In the recent years, researches on drugs for prostate cancer have received more attention than ever before. This article reviews the mechanism and efficacy of such prostate cancer drugs as bicalutamide, medroxyprogesterone acetate, megestrol acetate, flutamide and so on, as well as the clinical data and clinical uses of calcitriol analogue EB1089, SR233377, etc.
Androgen Antagonists ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Goserelin ; therapeutic use ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; Sulfonamides ; therapeutic use ; Suramin ; therapeutic use ; Thioxanthenes ; therapeutic use

Purinergic receptors play an important role in regulating gastrointestinal (GI) motility. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate GI smooth muscle activity. We studied the functional roles of external adenosine 5′-triphosphate (ATP) on pacemaker activity in cultured ICCs from mouse small intestines by using the whole-cell patch clamp technique and intracellular Ca²⁺ ([Ca²⁺]ᵢ) imaging. External ATP dose-dependently depolarized the resting membrane and produced tonic inward pacemaker currents, and these effects were antagonized by suramin, a purinergic P2 receptor antagonist. ATP-induced effects on pacemaker currents were suppressed by an external Na⁺-free solution and inhibited by the nonselective cation channel blockers, flufenamic acid and niflumic acid. The removal of external Ca²⁺ or treatment with thapsigargin (inhibitor of Ca²⁺ uptake into endoplasmic reticulum) inhibited the ATP-induced effects on pacemaker currents. Spontaneous [Ca²⁺]ᵢ oscillations were enhanced by external ATP. These results suggest that external ATP modulates pacemaker activity by activating nonselective cation channels via external Ca²⁺ influx and [Ca²⁺]ᵢ release from the endoplasmic reticulum. Thus, it seems that activating the purinergic P2 receptor may modulate GI motility by acting on ICCs in the small intestine.
Adenosine ; Adenosine Triphosphate ; Animals ; Endoplasmic Reticulum ; Flufenamic Acid ; Interstitial Cells of Cajal ; Intestine, Small ; Membranes ; Mice ; Muscle, Smooth ; Niflumic Acid ; Pacemaker, Artificial ; Receptors, Purinergic ; Receptors, Purinergic P2 ; Suramin ; Thapsigargin