Small molecule, oligonucleotide-based telomerase template inhibition in combination with cytolytic therapy in an in vitro androgen-independent prostate cancer model

Urologic Oncology
Benjamin K CanalesKenneth S Koeneman

Abstract

Determine the efficacy and timing of small molecule oligonucleotide-based inhibitors to the enzyme telomerase in an in vitro model of androgen-independent, osseous prostate cancer. Telomerase was inhibited in prostate cancer cell lines C4-2/C4-2B and in controls by using small molecule antisense oligonucleotide-based inhibitors alone or in various combinations of small-dose Taxotere (sanofi-aventis, Bridgewater, NJ) and/or conditionally replication competent adenovirus (AD-BSP-E1a). After transfection and proliferation, telomerase telomeric repeat amplification protocol and telomere restriction fragment assays were performed, with specific times for evaluating telomere length. Specimens were stained for analysis with hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and prostate-specific antigen (PSA). C4-2/C4-2B cell lines had the shortest initial mean telomere length (approximately 2.5 kilobase [kb]) compared to PC-3 (approximately 5.5 kb). Dose-dependent inhibition of telomerase activity was seen using match oligonucleotide-based inhibitors to telomerase (50% inhibitory concentration 3-5 nm), whereas mismatch compound showed no telomerase inhibiti...Continue Reading

References

Mar 1, 1991·Mutation Research·C B Harley
May 31, 1990·Nature·C B HarleyC W Greider
Aug 30, 1990·Nature·N D HastieR C Allshire
Jan 1, 1986·Cold Spring Harbor Symposia on Quantitative Biology·H J Cooke, B A Smith
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R K MoyzisJ R Wu
Oct 18, 1972·Nature: New Biology·J D Watson
Nov 11, 1995·Lancet·L A LangfordJ W Shay
Sep 1, 1995·Science·J FengJ Yu
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·T de Lange
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·C M CounterC B Harley
Mar 1, 1997·The Journal of Urology·Y LinY Kubota
May 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J A McCaffreyD F Bajorin
Jul 4, 1997·Journal of Medicinal Chemistry·D SunL H Hurley
Apr 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J W Shay, S Bacchetti
Aug 1, 1997·Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B·B V KallakuryJ S Ross
Feb 12, 1998·Genes & Development·L HarringtonM O Robinson
Feb 26, 1998·Cell·B van SteenselT de Lange
May 25, 1999·Cell·J D GriffithT de Lange
Aug 10, 1999·Nature·W C HahnR A Weinberg
Sep 29, 1999·Genes & Development·X ZhangM O Robinson
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·B HerbertD R Corey
Feb 12, 2000·Molecular and Cellular Biology·A SmogorzewskaT de Lange
Apr 1, 2000·The Journal of Biological Chemistry·M M OuelletteW E Wright
Apr 29, 2000·The Journal of Biological Chemistry·K E HuffmanW E Wright
May 12, 2000·Biochimica Et Biophysica Acta·B F Baker, B P Monia
Nov 18, 2000·Chemical Research in Toxicology·D R Corey
Mar 21, 2001·Human Molecular Genetics·J W ShayW E Wright
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·M M KimE H Blackburn
Feb 14, 2002·Differentiation; Research in Biological Diversity·Nicholas R ForsythJerry W Shay
Feb 19, 2002·Oncogene·Calvin B Harley
Feb 19, 2002·Oncogene·Brittney-Shea HerbertBrittney Shea-Herbert

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Citations

Aug 3, 2010·Pathology, Research and Practice·Dilek Ertoy BaydarBora Gurel
Apr 3, 2007·The Veterinary Journal·Lubna Nasir
Nov 13, 2009·International Journal of Cancer. Journal International Du Cancer·Calin O MarianJerry W Shay
Jul 4, 2006·Experimental Gerontology·Helen B Fleisig, Judy M Y Wong
Mar 7, 2009·Biochimica Et Biophysica Acta·Calin O Marian, Jerry W Shay
Jan 13, 2010·Chemistry & Biology·David R Corey
Oct 15, 2013·Cancer Discovery·Jerry W Shay

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