Dichloroacetate is an antimetabolite that antagonizes acetate and deprives cancer cells from its benefits: A novel evidence-based medical hypothesis.

Dichloroacetate (DCA) is a promising safe anticancer drug that cured a patient with chemoresistant non-Hodgkin's lymphoma and treated lactic acidosis effectively. The well-known mechanism of DCA action is through stimulating Krebs cycle (stimulating pyruvate dehydrogenase via inhibiting pyruvate dehydrogenase kinase). This prevents lactate formation (Warburg effect) depriving cancer cells of lactate-based benefits e.g. angiogenesis, chemoresistance and radioresistance. Here, we introduce novel evidence-based hypotheses to explain DCA-induced anticancer effects. On pharmacological and biochemical bases, we hypothesize that DCA is a structural antagonist of acetate competing with it for target enzymes and biological reactions. We hypothesize that DCA exerts its anticancer effects via depriving cancer of acetate benefits. We hypothesize also that acetate is an antidote of DCA capable of treating DCA toxicity. Many reports support our hypotheses. Acetate is vital for cancer cells (tumors depend on acetate) and DCA is structurally similar to acetate. DCA exerts opposite effects to acetate. Acetate caused a decrease in serum potassium, phosphorus and glucose, and an increase in serum lactate, citrate, free fatty acids and ketone bodies (serum acetoacetate and beta-hydroxybutyrate levels). Acetate decreased the proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart. DCA produced quite opposite effects. Intravenous infusion of acetate produced metabolic alkalemia while DCA caused minimal effects on acid-base status. Acetate is important for cancer cells metabolism and survival as elevated acetate can drive resistance to targeted cancer treatments. Acetate is required for epidermal growth factor receptor vIII mutation in lethal brain tumors. Experimentally, DCA inhibited acetate oxidation in hearts of normal rats and reversed inhibitory effects of acetate on the oxidation of glucose. During presence of DCA with no glucose in heart perfusions with [1-14C]acetate, DCA decreased the specific radioactivity of acetyl CoA and its product citrate. This proves our hypotheses that DCA is an antimetabolite that antagonizes acetate for vital reactions in cancer cells. Acetate may be used as an antidote to combat DCA toxicity.

Preparation and evaluation of Salmonella Enteritidis antigen conjugated with nanogold for screening of poultry flocks.

AIM: The present work aimed to develop lateral flow immunochromatographic strip (ICS) test for detection of Salmonella Enteritidis (SE) specific antibodies in chicken sera. MATERIALS AND METHODS: A rapid lateral flow immunochromatographic test (LFIT) has been developed, in which SE Group D antigen labeled with the gold chloride molecules laid on the conjugate pad. Staphylococcus aureus protein A was used as capture antibody at the test line (T) of a nitrocellulose (NC) membrane and anti-SE antigen-specific rabbit antibodies were used as capture antibody at the control line (C) of the NC strip in the lateral flow layout device. RESULTS: Using the developed LFIT, the minimal amount of SE-specific antibodies that can be detected in chicken serum sample was 1427 enzyme-linked immunosorbent assay (ELISA) unit/100 µl that was equal to 0.1 µg (Ab)/100 µl sample. 100 suspected serum samples collected from a poultry flock were tested with the prepared SE-LFIT kits and the locally prepared stained Salmonella antigen, and the results were compared with those obtained from examination of these samples with Salmonella Group D antibody ELISA kit as the gold standard test. The sensitivity, specificity, and accuracy of the prepared SE-LFIT antigen kits were 94.4%, 90%, and 94%, respectively, while those obtained with stained Salmonella antigen were 88.8%, 90%, and 89%, respectively. CONCLUSION: The developed test is a simple field rapid test of high sensitivity, specificity, and accuracy that can improve and facilitates rapid field surveillance of salmonellosis among chickens.