Targeting signal transducer and activator of transcription 3 with G-quartet oligonucleotides: a potential novel therapy for head and neck cancer

Molecular Cancer Therapeutics
Naijie JingDavid J Tweardy

Abstract

Signal transducer and activator of transcription 3 (Stat3) is a critical mediator of oncogenic signaling activated frequently in many types of human cancer where it contributes to tumor cell growth and resistance to apoptosis. Stat3 has been proposed as a promising target for anticancer drug discovery. Recently, we developed a series of G-quartet oligodeoxynucleotides (GQ-ODN) as novel and potent Stat3 inhibitors, which significantly suppressed the growth of prostate and breast tumors in nude mice. In the present study, we showed that GQ-ODN specifically inhibited DNA-binding activity of Stat3 as opposed to Stat1. Computer-based docking analysis revealed that GQ-ODN predominantly interacts with the SH2 domains of Stat3 homodimers to destabilize dimer formation and disrupt DNA-binding activity. We employed five regimens in the treatment of nude mice with tumors of head and neck squamous cell carcinoma (HNSCC): placebo, paclitaxel, GQ-ODN T40214, GQ-ODN T40231, and T40214 plus paclitaxel. The mean size of HNSCC tumors over 21 days only increased by 1.7-fold in T40214-treated mice and actually decreased by 35% in T40214 plus paclitaxel-treated mice whereas the mean size of HNSCC tumors increased 9.4-fold in placebo-treated mice in...Continue Reading

References

Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·J R WyattD J Ecker
Jan 1, 1994·Annual Review of Biophysics and Biomolecular Structure·J R Williamson
Mar 8, 1996·The Journal of Biological Chemistry·J S BishopN Chaudhary
Jan 1, 1996·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·D T WongR B Donoff
Dec 18, 1998·The Journal of Biological Chemistry·N Jing, M E Hogan
Jun 11, 1999·Current Opinion in Structural Biology·D E Gilbert, J Feigon
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Sep 3, 1999·The Journal of Biological Chemistry·P J BatesD M Miller
Feb 1, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·T L WallaceP A Cossum
Apr 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·J R GrandisJ D Kim
Jun 13, 2000·Oncogene·T BowmanR Jove
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Dec 9, 2003·DNA and Cell Biology·Naijie JingDavid J Tweardy
Feb 18, 2004·Nature Reviews. Cancer·Hua Yu, Richard Jove
Dec 16, 2004·Seminars in Oncology·Michael Fanucchi, Fadlo R Khuri
Mar 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alphonse G TaghianSimon N Powell
Jun 7, 2005·Nature Medicine·James E Darnell
Aug 17, 2005·Current Pharmaceutical Design·Naijie JingDavid J Tweardy

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Citations

Feb 4, 2014·Bioorganic & Medicinal Chemistry·Han ChenNaijie Jing
Sep 17, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yongli GuanNaijie Jing
Oct 3, 2006·Nucleic Acids Research·Sarah BurgeStephen Neidle
Dec 25, 2009·Retrovirology·Evelyn M KilareskiBrian Wigdahl
Jul 21, 2012·OncoTargets and Therapy·Adetola L Shodeinde, Beverly E Barton
Apr 30, 2011·Future Medicinal Chemistry·Daniela MasciocchiDaniela Barlocco
Sep 29, 2011·Genetics and Molecular Research : GMR·B JiangG Huang
Jul 7, 2007·Expert Opinion on Therapeutic Targets·Hongwei Gao, Peter A Ward
Oct 6, 2006·Expert Review of Anticancer Therapy·Ralph PriesBarbara Wollenberg
Dec 5, 2008·Expert Opinion on Investigational Drugs·Peibin Yue, James Turkson
May 21, 2009·Experimental and Molecular Pathology·Paula J BatesJohn O Trent
Oct 1, 2006·Drug Discovery Today. Technologies·Michele S Redell, David J Tweardy
Mar 8, 2007·Annals of the New York Academy of Sciences·Bharat B AggarwalHaruyo Ichikawa
Aug 5, 2008·Chembiochem : a European Journal of Chemical Biology·Thorsten Berg
Jan 21, 2010·International Journal of Cancer. Journal International Du Cancer·Zu-Yin YuYu-Wen Cong
Mar 25, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Biao WangYifu Guan
Sep 24, 2013·JAK-STAT·Malabika Sen, Jennifer R Grandis
Sep 24, 2013·JAK-STAT·Remi FagardFanny Baran-Marszak
Jul 16, 2008·Seminars in Cell & Developmental Biology·Gabriella RegisValeria Poli
Nov 23, 2006·Chemistry & Biology·Jochen SchustThorsten Berg
Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Neeraj KumariAnant Narayan Bhatt
Oct 9, 2016·European Journal of Medicinal Chemistry·Wenda ZhangLingyi Kong
Jul 27, 2011·Chemical Society Reviews·Gavin W Collie, Gary N Parkinson
Nov 24, 2007·Journal of Computer-aided Molecular Design·Qiqing Zhu, Naijie Jing
Oct 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Carolina RoxoAnna Pasternak
Oct 3, 2018·Pharmaceuticals·Philisiwe Fortunate MolefeAbidemi Paul Kappo
Mar 14, 2020·Genetics and Molecular Biology·Sundas ArshadFazeeha Amjad
Jan 9, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nobuaki KobayashiHidekazu Shirota
Nov 2, 2019·Cancers·Yue-Ting K LauJennifer R Grandis
Jun 7, 2020·Cancers·Angela MinerviniFrancesco Albano

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