title: High Throughput Screening for Colorectal Cancer Specific Compounds.
abstract: The development of new anti-cancer therapeutic agents is necessary to improve antitumor efficacy and reduce toxicities. Here we report using a systematic anticancer drug screening approach we developed previously, to concurrently screen colon and glioma cancer cell lines for 2000 compounds with known bioactivity and 1920 compounds with unknown activity. The hits specific to each tumor cell line were then selected, and further tested with the same cells transfected with EGFP (Enhanced Green Fluorescent Protein) alone. By comparing the percentage of signal reduction from the same cells transfected with the sensor-conjugated reporter system; hits preferably causing apoptosis were identified. Among the known lead compounds, many cardiac glycosides used as cardiotonic drugs were found to effectively and specifically kill colon cancer cells, while statins (hypolipidemic agents) used as cholesterol lowering drugs were relatively more effective in killing glioma cells.
authors.affiliation: VUIIS, Vanderbilt University, Nashville, TN 37232, USA. Jingping.Xie@vanderbilt.edu.
authors.forename: Jingping
authors.initials: J
authors.lastname: Xie
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.affiliation: VUIIS, Vanderbilt University, Nashville, TN 37232, USA. John.Gore@vanderbilt.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002301:Cardiac Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D057166:High-Throughput Screening Assays; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D000960:Hypolipidemic Agents
references.citation: Anticancer Agents Med Chem. 2011 Mar;11(3):307-14
references.pmid: 21443504
references.citation: Expert Rev Anticancer Ther. 2011 May;11(5):781-9
references.pmid: 21554053
references.citation: PLoS One. 2011;6(8):e23852
references.pmid: 21909365
references.citation: CA Cancer J Clin. 1996 May-Jun;46(3):185-92
references.pmid: 8646547
references.citation: Nat Rev Drug Discov. 2011 Jun 24;10(7):507-19
references.pmid: 21701501
references.citation: Acta Reumatol Port. 2006 Jul-Sep;31(3):215-24
references.pmid: 17094333
references.citation: Oncologist. 2000;5(3):185-98
references.pmid: 10884497
references.citation: J Nutr. 2001 Jan;131(1):158S-160S
references.pmid: 11208954
references.citation: J Biol Chem. 2004 Dec 31;279(53):56053-60
references.pmid: 15509580
references.citation: Clin Cancer Res. 2003 Jan;9(1):10-9
references.pmid: 12538446
references.citation: FEBS Lett. 2004 Apr 9;563(1-3):151-4
references.pmid: 15063740
references.citation: J Pharmacol Exp Ther. 2011 Jan;336(1):3-8
references.pmid: 20739456
references.citation: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555-9
references.pmid: 1699228
references.citation: N Engl J Med. 2009 Dec 17;361(25):2449-60
references.pmid: 20018966
references.citation: Biochem Pharmacol. 2003 Dec 1;66(11):2223-39
references.pmid: 14609747
references.citation: Drug Discov Today. 2013 Mar;18(5-6):211-7
references.pmid: 23131208
references.citation: Chembiochem. 2013 Aug 19;14(12):1494-503
references.pmid: 23881799
references.citation: N Engl J Med. 2012 Nov 8;367(19):1792-802
references.pmid: 23134381
references.citation: Cancer Res. 2000 Jul 15;60(14):3838-47
references.pmid: 10919658
references.citation: Curr Med Chem. 2012;19(5):627-46
references.pmid: 22204337
references.citation: Planta Med. 2011 May;77(7):726-9
references.pmid: 21049400
references.citation: Cell Tissue Res. 2002 Dec;310(3):257-70
references.pmid: 12457224
references.citation: Carcinogenesis. 2005 May;26(5):883-91
references.pmid: 15705602
references.citation: Int J Cancer. 1988 Feb 15;41(2):287-96
references.pmid: 3338874
references.citation: Anticancer Res. 2010 Sep;30(9):3611-9
references.pmid: 20944144