Study Data from Slovak Academy of Sciences Update Knowledge of Xenografts (Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts)
By a News Reporter-Staff News Editor at Cancer Weekly -- New research on Biotechnology is the subject of a report. According to news reporting out of Bratislava, Slovakia, by NewsRx editors, research stated, "Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment."
Our news journalists obtained a quote from the research from the Slovak Academy of Sciences, "Carnosine (beta-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1 alpha and CA IX and/or altered CA IX function. The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1 alpha and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Carnosine increased the expression levels of HIF-1 alpha and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX and anion exchanger 2 in the presence of carnosine. Our results indicate that interaction of carnosine with CA IX leads to conformational changes of CA IX and impaired formation of its metabolon, which in turn disrupts CA IX function."
According to the news editors, the research concluded: "These findings suggest that carnosine could be a promising anticancer drug through its ability to attenuate the activity of CA IX."
For more information on this research see: Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts. BMC Cancer, 2014;14():1-13. BMC Cancer can be contacted at: Biomed Central Ltd, 236 Grays Inn Rd, Floor 6, London WC1X 8HL, England. (BioMed Central - www.biomedcentral.com/; BMC Cancer - www.biomedcentral.com/bmccancer/)
Our news journalists report that additional information may be obtained by contacting Z. Ditte, Slovak Academy Sci, Center Mol Med, Bratislava 83101, Slovakia. Additional authors for this research include P. Ditte, M. Labudova, V. Simko, F. Iuliano, M. Zatovicova, L. Csaderova, S. Pastorekova and J. Pastorek (see also Biotechnology).
Keywords for this news article include: Bratislava, Slovakia, Europe, Biotechnology, Xenograft, Xenotransplantion
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