title: T-oligos inhibit growth and induce apoptosis in human ovarian cancer cells.
abstract: Ovarian cancer remains a leading cause of death among women worldwide, and current treatment regimens for advanced disease are inadequate. Oligonucleotides with sequence homology to telomeres (called T-oligos) have been shown to mimic DNA damage responses in cells and induce cytotoxic effects in certain tumor cell lines. We studied the effects of 2 distinct 16 mer T-oligos in 4 human ovarian epithelial carcinoma cell lines. A T-oligo with perfect homology to the telomere overhang region demonstrated some cytotoxic activity in half of the cell lines. A G-rich T-oligo derivative showed more potency and broader cytotoxic activity in these lines than the parental T-oligo. Activation of apoptotic pathways in ovarian cancer cells by exposure to the T-oligo was demonstrated by multiple independent assays. T-oligo was shown to have additive, or more than additive, activity in combination with 2 different histone deacetylase drugs currently in clinical testing. T-oligos may therefore provide a new and tumor-targeted approach to ovarian cancers.
authors.affiliation: Cancer Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Sibaji
authors.initials: S
authors.lastname: Sarkar
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faller
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D000077216:Carcinoma, Ovarian Epithelial; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018716:Molecular Mimicry; D058990:Molecular Targeted Therapy / Q000379:methods*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D009841:Oligonucleotides