title: Selective inhibition of human carbonic anhydrase IX in Xenopus oocytes and MDA-MB-231 breast cancer cells.
abstract: Human carbonic anhydrase IX (CA IX) is overexpressed in the most aggressive and invasive tumors. Therefore, CA IX has become the promising antitumor drug target. Three inhibitors have been shown to selectively and with picomolar affinity inhibit human recombinant CA IX. Their inhibitory potencies were determined for the CA IX, CA II, CA IV and CA XII in Xenopus oocytes and MDA-MB-231 cancer cells. The inhibition IC50value of microelectrode-monitored intracellular and extracellular acidification reached 15 nM for CA IX, but with no effect on CA II expressed in Xenopus oocytes. Results were confirmed by mass spectrometric gas analysis of lysed oocytes, when an inhibitory effect on CA IX catalytic activity was found after the injection of 1 nM VD11-4-2. Moreover, VD11-4-2 inhibited CA activity in MDA-MB-231 cancer cells at nanomolar concentrations. This combination of high selectivity and potency renders VD11-4-2, an auspicious therapeutic drug for target-specific tumor therapy.
authors.affiliation: a Department of Biothermodynamics and Drug Design , Institute of Biotechnology, Vilnius University , Vilnius , Lithuania and.
authors.forename: Justina
authors.initials: J
authors.lastname: Kazokaitė
authors.affiliation: b Division of General Zoology , FB Biologie, TU Kaiserslautern , Kaiserslautern , Germany.
authors.forename: Samantha
authors.initials: S
authors.lastname: Ames
authors.affiliation: b Division of General Zoology , FB Biologie, TU Kaiserslautern , Kaiserslautern , Germany.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Becker
authors.affiliation: b Division of General Zoology , FB Biologie, TU Kaiserslautern , Kaiserslautern , Germany.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
authors.affiliation: a Department of Biothermodynamics and Drug Design , Institute of Biotechnology, Vilnius University , Vilnius , Lithuania and.
authors.forename: Daumantas
authors.initials: D
authors.lastname: Matulis
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D000071231:Carbonic Anhydrase IX / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015394:Molecular Structure; D009865:Oocytes / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000071231:Carbonic Anhydrase IX
keywords: Benzenesulfonamides; MDA-MB-231 cells; Xenopus oocytes; carbonic anhydrase IX