INVOLVEMENT OF POTASSIUM-IONS IN THE ACTION OF VARIOUS ANTINEOPLASTIC DRUGS ON THE GROWTH OF SACCHAROMYCES-CEREVISIAE

The involvement of potassium ions in the action of some antineoplastic drugs on the growth of Saccharomyces cerevisiae was studied by incubating yeast cells in the presence of drugs at various concentrations and KCl at concentrations of 50 mmol l-1 and 100 mmol l-1. The presence of 6.25-50 mug ml-1 amsacrine or melphalan alone in the culture medium had no significant effect on yeast growth. Addition of KCl significantly increased the sensitivity to these drugs. On the contrary, incubation of yeast cells with KCl had no effect on the cytotoxic action of doxorubicin, methotrexate or 5-fluorouracil

Molybdate modulates mitogen and cyclosporin responses of human peripheral blood lymphocytes

The trace element molybdenum (Mo) is an essential component of key physiological systems in animals, plants and microorganisms. The molybdate oxoanion MoO 4 2- has been demonstrated to cause diverse yet poorly understood biochemical and pharmacological effects, such as non-specific inhibition of phosphatases and stabilization of steroid receptors. This study aimed to investigate the effects of molybdate on the activation of human peripheral blood lymphocytes (hPBLs) ex vivo and its potential interaction with the widely used immunosuppressant drug cyclosporin A (CsA). Lymphocyte activation was evaluated by performing multiple experiments determining blastogenesis in cultured peripheral blood lymphocytes obtained from 5 healthy volunteers, following stimulation induced by phytohemagglutinin (PHA), in the absence or presence of 0.05-10mM sodium molybdate or/and 2.5-30μg/mL CsA. Blastogenesis was assessed by a morphometric assay based on the relative proportions of unactivated lymphocytes, activated lymphoblasts and cells with aberrant morphology after PHA-induced activation. Molybdate concentrations up to 1mM showed no effect on lymphocyte blastogenesis, while higher concentrations exerted immunosuppressive actions on cultured hPBLs. Co-administration of 0.1mM sodium molybdate with CsA, at doses up to 20μg/mL, induced no alteration in the response of cultured hPBLs to CsA. However, molybdate potentiated the immunosuppressive action of higher CsA concentrations, implying a likely dose-related synergistic interaction of the two agents in PHA-stimulated blood lymphocytes. These observations are indicative of the possible biological importance of molybdate oxoanions in the modulation of hPBL activation that may have pharmacological consequences during the therapeutic application of immunomodulatory drugs. © 2011 Elsevier GmbH

The heat shock response is dependent on the external environment and on rapid ionic balancing by pharmacological agents in Saccharomyces cerevisiae

Aims: To investigate whether non-preconditioned yeast cells survive under heat shock, when placed in growth medium originated from protected cells and to provide insights into the ionic contribution in the response. Methods and Results: The heat shock response was investigated by determining cell viability following exposure of yeast cells to 53°C for 30 min, either in the absence or presence of drugs. Preconditioning was performed by incubating the cultures at 37°C for 2 h. Under heat shock, non-preconditioned cell survival was significantly enhanced by the presence of the cell-free supernatant of resistant cultures. Addition of omeprazole or tetraethylammonium ions during the heat shock resulted in similar increases. Neither amiodarone nor mepivacaine showed any analogous effect. Omeprazole enhanced survival when added before the heat shock, while amiodarone exhibited a cytocidic action. Conclusions: Rapid balancing of ions may contribute to cell survival during heat shock, while survival under mild stress could probably be co-ordinated by additional events. Significance and Impact of the Study: Evidence is provided for the implication of the external environment and ionic homeostasis in the survival of yeast cells under unfavourable environmental conditions. This knowledge may be of importance in controlling both fermentation and therapeutic approaches

Cross-talk between cellular stress, cell cycle and anticancer agents: Mechanistic aspects

Environmental conditions such as temperature, radiation, hypoxia, nutrients and drugs stimulate the adaptive sensory and signaling machinery of the cell. This stress response may influence cell cycle regulation, cellular differentiation, oncogenic transformation, cell survival and apoptosis. The impact of the cytoprotective reprogramming in cancer pharmacology is presented by the recent extensive literature regarding the interplay between stress tolerance and anticancer drug effectiveness and resistance, relying on the dominating intrinsic pathways, which are simultaneously activated and regulate the death process either positively or negatively. This review presents the data that argue for the emergence of either common or specific mechanisms depending on the type, duration and severity of stress in all eukaryotic organisms from yeast to mammals. The understanding of the complexity and the balance between noxious and protective signal transduction pathways would contribute to a more explicit evaluation of the current therapeutic regiments and to the development of new leads targeting malignancy

Induction of morphological alterations by antineoplastic agents in yeast.

Saccharomyces cerevisiae was used as an alternative experimental model in order to investigate the effects of antineoplastic agents on eukaryotic cells. After being exposed to the most common clinically used antineoplastic agents, yeast cells were examined under the light microscope. Folate and pyrimidine antagonists, platinum derivatives, mitomycin C, actinomycin D and bleomycin induced alterations in yeast cellular morphology, which were not observed following treatment with drugs belonging to any category other than the antineoplastics, leading to the suggestion that these alterations could potentially be used as an experimental tool in pre-screening for new chemotherapeutic leads

Changes in histamine content following pharmacologically-induced mast cell degranulation in the rat conjunctiva

Compound 48/80 was applied into one eye of male Wistar rats and a drop of vehicle into the contralateral eye. Another group of rats received sodium cromoglycate in both eyes every 6 h for a period of 48 h. One eye was challenged with compound 48/80 30 min after the end of treatment with sodium cromoglycate. The eyes were monitored clinically and the histamine content of the conjunctiva was determined fluorometrically. The basal histamine levels in rat conjunctival homogenates were quantified. Pharmacologically-induced mast cell degranulation by a single application of 0.1 g ml-1 of compound 48/80 resulted in significant decreases of conjunctival histamine levels 1, 12 and 24 h after challenge. Sodium cromoglycate prevented the effect of compound 48/80 when administered into the eye prior to the challenge with the non-immunogenic histamine releaser. Upon termination of the application, the membrane stabilizer was unable to reverse the reduced histamine levels in the conjunctival homogenates. (C) 2000 Academic Press

RESPONSE OF SACCHAROMYCES-CEREVISIAE STRAINS TO ANTINEOPLASTIC AGENTS

The effect of several antineoplastic agents on Saccharomyces cerevisiae strains has been investigated. Minimum inhibitory concentration (MIC), minimum cytotoxic concentration (MCC) and median effective concentration (EC(50)) were determined to identify strains with inherent sensitivity to the agents tested. Several strains proved to be sensitive to the antimetabolites 5-fluorouracil and methotrexate as well as to doxorubicin and cis-platine. On the contrary m-amsacrine, procarbazine, vinca alcaloids, melphalan and hydroxyurea were inactive at concentrations up to 400 mu g ml(-1). The strain ATCC 2366, the most relatively sensitive to the agents tested, was used for studying the effect of treatment duration and of drug concentration on cell survival. Methotrexate and cis-platine, which according to MIC and MCC tests seemed ineffective for this strain, reduced survival significantly after 6 h of treatment. A correlation of the shape of the survival curves with MIC and MCC values was attempted

Antiphage activity in extracts of plants growing in Greece

Crude aqueous extracts of 255 plant taxa growing in various areas of Greece were screened for antiphage activity against 6 bacteriophages (T 1, T 2, T 4, T 7, MS 2 and ΦX 174). This laboratory model has been used for the initial detection of antiviral and/or antineoplastic activity. Thirty eight extracts showed antiphage activity against one or more of the bacterial viruses used. When the active extracts were tested in the presence of Tryptone Soya Broth, part of the antiphage activity remained in 7 extracts, whereas when tested in the presence of fresh human plasma, the antiphage activity was abolished, possibly due to the precipitation of the active compounds by tannins or related substances

Antibacteriophage properties of some Greek plant extracts

The ethanol extracts (70%) of 45 plants grown in Greece were screened for antibacteriophage properties against 6 bacteriophages: coliphages T-1, T-2, T-4, T-7, phi X174, and MS(2). Eight samples were found to induce a significant antiphage activity and can be used as material for further antiviral studies in vitro and in vivo