cyclic-gmp and Carcinoma--Ehrlich-Tumor

Ehrlich cell plasma membrane ferricyanide reductase activity increased in the presence of mastoparan, a generic activator of G proteins, using either whole cells or isolated plasma membrane-fractions. Agents that increase intracellular cAMP also increased the rate of ferricyanide reduction by Ehrlich cells. For the first time, evidence is shown on a modulation of plasma membrane redox system by cGMP. In fact, permeant analogs of cGMP, dibutyryl cGMP, and 8-bromo-cGMP increased the rate of ferricyanide reduction by the Ehrlich cell plasma membrane redox system. Furthermore, specific inhibition of cGMP-phosphodiesterases by dipyridamole was also accompanied by an enhancement in the rate of ferricyanide reduction. On the other hand, treatments expected to increase cytoplasmic Ca2+ concentrations were accompanied by a remarkable stimulation of the reductase activity. Taking all these data together, it seems that the Ehrlich cell plasma membrane redox system is under a multiple and complex regulation by different signal transduction pathways involving G proteins, cyclic nucleotides, and Ca2+ ions.

Topics: Animals; Bucladesine; Calcimycin; Calcium; Calcium-Transporting ATPases; Carcinoma, Ehrlich Tumor; Cell Membrane; Cyclic GMP; Dibutyryl Cyclic GMP; Enzyme Inhibitors; Female; Kinetics; Mice; NADH, NADPH Oxidoreductases; Neomycin; Oxidation-Reduction; Second Messenger Systems; Signal Transduction; Sphingosine; Thapsigargin

Topics: Animals; Calmodulin; Carcinoma, Ehrlich Tumor; Cell Division; Cell Line; Cyclic AMP; Cyclic GMP; Humans; Mice; Microtubules; Stomach Neoplasms; Trifluoperazine

A new polysaccharide compound (ACPS-R) has recently been isolated from the root of Actinidia Chinensis Planch. When given intraperitoneally to the transplantable tumor bearing mice at dose of 75-125 mg/kg, the tumor inhibition rate was more than 88.8% in Ehrilich ascitic cancer (EAC) or ascitic form of hepatoma (HepA) and more than 49.6% in solid hepatoma (HepS). The treatment effect of ACPS-R on EAC at dose of 15 mg/kg and 22.5 mg/kg, respectively. ACPS-R could also prolong the life of EAC-or P388-bearing mice, and increase the percentage of EAC-free mice. In addition, when ACPS-R was used in combination with 5-Fu, the antitumor effect was enhanced as compared with 5-Fu alone. A marked increase in cAMP levels and cAMP/cGMP ratio of spleen of EAC-bearing mice were observed after treatment of ACPS-R. The increase of both parameters nearly reached the normal levels of healthy mice. The increases of cAMP, cAMP/cGMP and tumor remission had statistical significance. It showed an intermediate inhibitory effect of ACPS-R on DNA synthesis by incorporating 3H-TdR into EAC cells. The results indicated that ACPS-R acts as a new antitumor polysaccharide, and the treatment effect of Actinidia root in folk medicine is probably related to ACPS-R.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cyclic AMP; Cyclic GMP; Drugs, Chinese Herbal; Liver Neoplasms, Experimental; Mice; Mice, Inbred DBA; Polysaccharides; Spleen

A phosphorylation of endogenous acceptor protein(s) has been demonstrated to occur in membraneous vesicles prepared from Ehrlich ascites tumour cells. The reaction was catalyzed by endogenous protein kinase in the presence of exogenous (gamma32P)ATP. A considerable increase of the specific protein kinase activity took place when the plasma membrane preparation was subjected to a further gradient centrifugation in Dextran T 150. This was done in the presence of a slightly alkaline phosphate buffer containing Mg-ions which resulted in the formation of a well defined vesicular preparation at density 1.035 in the gradient. The apparent Km and Vmax for the reaction with vesicles and exogenous (gamma32P)ATP were determined and found to be 0.022 mM and 0.23 nmol x mg-1 x 10 min-1, respectively. Neither cyclic AMP nor cyclic GMP did stimulate the protein kinase-catalyzed reaction. Instead, a clear inhibition of the reaction by the cyclic nucleotides was unexpectedly registered. Adenosine at 0.5 mM also inhibited the reaction. Calcium ions were inhibitory at all concentrations tested in the presence of a fixed (gamma32P)ATP/Mg2+ ratio. When Mg-ions were stoichiometrically replaced by Ca-ions practically no activity was observed.

Topics: Adenosine; Adenosine Triphosphate; Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Centrifugation, Density Gradient; Chemical Fractionation; Cyclic AMP; Cyclic GMP; Dextrans; Male; Membrane Proteins; Mice; Phosphorylation; Protein Kinases; Subcellular Fractions

Changes in the concentration of cyclic AMP as well as cyclic GMP were measured in different murine tumors and in human tumors of varying malignancy. The quotient of cAMP and cGMP seems to be an important parameter for the molecular-biological derangement. Because of the recently much discussed importance of cAMP and cGMP in the immune defence the changes in the concentration of both nucleotides were measured in the T-lymphocytes of tumor patients. Significant changes occurred in patients with malignant melanoma. Investigations of the stimulatibility of the cAMP and cGMP levels revealed a diminished activatibility of the cAMP level and a higher stimulatibility of the cGMP level in the T-lymphocytes of patients with malignant melanoma as compared with those of the controls. On the basis of the working hypothesis that there is a causal relationship between the deranged dualism of cAMP and cGMP in the T-lymphocytes and the failure of the immunological tumor cell defence, an increase in the cAMP level is offered as a possible therapy. Therapeutic results in tumor-bearing mice and first results in melanoma patients are discussed.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cyclic AMP; Cyclic GMP; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Melanoma; Mice; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Nevus; Skin; Skin Neoplasms; T-Lymphocytes; Time Factors

One hundred and sixty-one purine analogs and derivatives were tested for their ability to inhibit ten parameters of purine metabolism in Ehrlich ascites tumor cells incubated in vitro with radioactive hypoxanthine. Sixty-seven compounds were inhibitory against at least one parameter and 30 were inhibitory against two or more.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Carcinoma, Ehrlich Tumor; Cyclic GMP; Energy Metabolism; Glutamine; Guanine Nucleotides; Guanosine Triphosphate; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; In Vitro Techniques; Inosine Nucleotides; Ketone Oxidoreductases; Ligases; Lyases; Mice; Purines