G-quartet oligonucleotides: a new class of signal transducer and activator of transcription 3 inhibitors that suppresses growth of prostate and breast tumors through induction of apoptosis

Cancer Research
Naijie JingDavid J Tweardy

Abstract

Stat3 is a signaling molecular and oncogene activated frequently in many human malignancies including the majority of prostate, breast, and head and neck cancers; yet, no current chemotherapeutic approach has been implemented clinically that specifically targets Stat3. We recently developed G-rich oligodeoxynucleotides, which form intramolecular G-quartet structures (GQ-ODN), as a new class of Stat3 inhibitor. GQ-ODN targeted Stat3 protein directly inhibiting its ability to bind DNA. When delivered into cells using polyethyleneimine as vehicle, GQ-ODN blocked ligand-induced Stat3 activation and Stat3-mediated transcription of antiapoptotic genes. To establish the effectiveness of GQ-ODN as a potential new chemotherapeutic agent, we systemically administered GQ-ODN (T40214 or T40231) plus polyethyleneimine or polyethyleneimine alone (placebo) by tail-vein injection into nude mice with prostate and breast tumor xenografts. Whereas the mean volume of breast tumor xenografts in placebo-treated mice increased >7-fold over 18 days, xenografts in the GQ-ODN-treated mice remained unchanged. Similarly, whereas the mean volume of prostate tumor xenografts in placebo-treated mice increased 9-fold over 10 days, xenografts in GQ-ODN-treated...Continue Reading

References

Nov 1, 1989·American Journal of Clinical Pathology·W E SchreiberM R Pudek
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
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·J F BrombergJ E Darnell
Jan 23, 1997·Nature·A J MinnC B Thompson
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·K TakedaS Akira
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·S L SchendelJ C Reed
Sep 12, 1997·Science·J E Darnell
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
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
Feb 13, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J F Bromberg
May 2, 2002·Cell·John J O'SheaRobert D Schreiber
Dec 9, 2003·DNA and Cell Biology·Naijie JingDavid J Tweardy

❮ Previous
Next ❯

Citations

Nov 24, 2007·Journal of Computer-aided Molecular Design·Qiqing Zhu, Naijie Jing
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
Jan 1, 2013·Nucleic Acids Research·Anh Tuân Phan, Ngoc Quang Do
Jun 3, 2005·Anti-cancer Drugs·Naijie Jing, David J Tweardy
Dec 25, 2009·Retrovirology·Evelyn M KilareskiBrian Wigdahl
Dec 7, 2013·Journal of Hematology & Oncology·Muhammad FurqanDelong Liu
Feb 14, 2008·PloS One·Jeffrey A AltenDavid J Tweardy
Apr 12, 2014·Cancers·Jennifer L BishopAmina Zoubeidi
Sep 14, 2013·Nucleic Acids Research·Ting-Yuan TsengTa-Chau Chang
Oct 25, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tarek ShalabyMichael Grotzer
Dec 5, 2008·Expert Opinion on Investigational Drugs·Peibin Yue, James Turkson
Jul 15, 2011·Expert Opinion on Investigational Drugs·Arun K Mankan, Florian R Greten
Mar 20, 2012·Journal of Drug Targeting·Markus Düchler
Mar 1, 2006·Expert Opinion on Biological Therapy·Rebecca J LeemanJennifer Rubin Grandis
May 21, 2009·Experimental and Molecular Pathology·Paula J BatesJohn O Trent
Feb 1, 2009·Clinical and Translational Science·Ana MoranDavid J Tweardy
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
Nov 11, 2006·IDrugs : the Investigational Drugs Journal·Letitia Perry, Andrew Balfe
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 19, 2011·Biophysical Journal·Christopher Jacques LechAnh Tuân Phan
Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Neeraj KumariAnant Narayan Bhatt
Mar 6, 2007·The Journal of Allergy and Clinical Immunology·Weiguo Chen, Gurjit K Khurana Hershey
Mar 17, 2006·Antiviral Research·Paul F TorrenceJohn D Morrey
May 18, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Stephen Y Lai, Faye M Johnson

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis