BACKGROUND: 2´-Deoxy-5-fluorouridylyl-(5´-5´)-3´-C-ethynylcytidine [5-FdU(5´-5´)ECyd] and 3´-C-ethynylcytidinylyl-(5´->1-O)-2-O-octadecyl-sn-glycerylyl-(3-Ο->5´)-2´-deoxy-5-fluorouridine [ECyd-lipid-5-FdU] are antitumor active duplex drugs and these heterodinucleoside phosphate analogues could be cleaved in vivo by wide-spread phosphodiesterases into different antitumor active antimetabolites. METHODS: We cultured breast MCF-7, MDA-MB-231 and ovarian OVCAR-29 and OAW-42 cancer cell lines and used the luminometric measuring of the ATP tumor chemosensitivity assay to assess the in vitro activity of 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU in comparison to standard single cytostatic agents and combinations thereof currently used in anticancer therapies. To allow comparison between samples and different regimens IndexSUM was determined based on the percentage tumor cell growth inhibition at each test drug concentration. Additionally, the cytostatic efficacy of 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU was evaluated at a minimum of five concentrations at 10 fold dilutions using 60 human tumor cell lines including ovarian and breast cancer cell lines from the National Cancer Institute (USA). RESULTS: 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU have a high cytostatic efficacy reaching 50% tumor cell growth inhibition at concentrations ranging between nano- and micomolar. IndexSum values for broad range efficacy in MCF-7 breast cancer cells were comparable to values obtained for standard drug combinations. Higher cytostatic efficacy was observed in MDA-MB-231 cells. CONCLUSION: The duplex drugs 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU represent potential new chemotherapeutic drugs for breast and ovarian cancer cells which are comparable to currently used drug combinations and more potent in comparison to some monocytostatica used in cancer therapy.
BACKGROUND: 2´-Deoxy-5-fluorouridylyl-(5´-5´)-3´-C-ethynylcytidine [5-FdU(5´-5´)ECyd] and 3´-C-ethynylcytidinylyl-(5´->1-O)-2-O-octadecyl-sn-glycerylyl-(3-Ο->5´)-2´-deoxy-5-fluorouridine [ECyd-lipid-5-FdU] are antitumor active duplex drugs and these heterodinucleoside phosphate analogues could be cleaved in vivo by wide-spread phosphodiesterases into different antitumor active antimetabolites. METHODS: We cultured breast MCF-7, MDA-MB-231 and ovarian OVCAR-29 and OAW-42 cancer cell lines and used the luminometric measuring of the ATPtumor chemosensitivity assay to assess the in vitro activity of 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU in comparison to standard single cytostatic agents and combinations thereof currently used in anticancer therapies. To allow comparison between samples and different regimens IndexSUM was determined based on the percentage tumor cell growth inhibition at each test drug concentration. Additionally, the cytostatic efficacy of 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU was evaluated at a minimum of five concentrations at 10 fold dilutions using 60 humantumor cell lines including ovarian and breast cancer cell lines from the National Cancer Institute (USA). RESULTS:5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU have a high cytostatic efficacy reaching 50% tumor cell growth inhibition at concentrations ranging between nano- and micomolar. IndexSum values for broad range efficacy in MCF-7 breast cancer cells were comparable to values obtained for standard drug combinations. Higher cytostatic efficacy was observed in MDA-MB-231 cells. CONCLUSION: The duplex drugs 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU represent potential new chemotherapeutic drugs for breast and ovarian cancer cells which are comparable to currently used drug combinations and more potent in comparison to some monocytostatica used in cancer therapy.
Authors: I V Bijnsdorp; R A Schwendener; H Schott; S Schott; I Fichtner; R J Honeywell; N Losekoot; A C Laan; G J Peters Journal: Nucleic Acids Symp Ser (Oxf) Date: 2008
Authors: D H Horber; R M Cattaneo-Pangrazzi; P von Ballmoos; H Schott; P S Ludwig; S Eriksson; I Fichtner; R A Schwendener Journal: J Cancer Res Clin Oncol Date: 2000-06 Impact factor: 4.553
Authors: Federica Di Nicolantonio; Louise A Knight; Pauline A Whitehouse; Stuart J Mercer; Sanjay Sharma; Peter A Charlton; David Norris; Ian A Cree Journal: Mol Cancer Ther Date: 2004-12 Impact factor: 6.261
Authors: P E Andreotti; I A Cree; C M Kurbacher; D M Hartmann; D Linder; G Harel; I Gleiberman; P A Caruso; S H Ricks; M Untch Journal: Cancer Res Date: 1995-11-15 Impact factor: 12.701
Authors: Sarah Schott; Markus Wallwiener; Beate Kootz; Harald Seeger; Tanja Fehm; Hans Neubauer Journal: Invest New Drugs Date: 2011-05-21 Impact factor: 3.850
Authors: Jürgen Weinreich; Sarah Schott; Ingmar Königsrainer; Derek Zieker; Alfred Königsrainer; Herbert Schott Journal: Invest New Drugs Date: 2010-07-02 Impact factor: 3.850
Authors: Sarah Schott; Pauline Wimberger; Barbara Klink; Konrad Grützmann; Julian Puppe; Ulrike Sophie Wauer; Daniel Martin Klotz; Evelin Schröck; Jan Dominik Kuhlmann Journal: Oncotarget Date: 2017-08-14