Abstract
(5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative, is a low-toxicity immunosuppressant in Phase I clinical trials. Here, we demonstrate that LLDT-8 displays broad-spectrum, potent (nanomolar level IC(50)s) antitumor activity, and induces S-phase cell-cycle arrest and apoptosis in vitro. Notably, LLDT-8 effectively overcomes multidrug resistance mediated by P-glycoprotein. In vivo, LLDT-8 demonstrates potent antitumor activity, particularly against human ovarian cancer 3AO and prostate cancer PC-3 xenografts in nude mice. The antitumor activity of LLDT-8 is achieved by virtue of its general inhibition of gene transcription. Our results indicate that LLDT-8 is a novel transcription inhibitor with potential for cancer therapy, particularly for cancers with drug resistance mediated by P-glycoprotein.
References
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·H M Sobell
Jan 1, 1995·Investigational New Drugs·D J Adams, V C Knick
Dec 15, 1996·Experimental Cell Research·A LerescheJ M Gottesfeld
Dec 31, 1997·Molecular and Cellular Biology·C Koumenis, A Giaccia
Apr 17, 1999·The Journal of Biological Chemistry·N G TheodorakisA De Maio
Oct 19, 1999·Oncogene·R H te PoeleS P Joel
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Nov 9, 2001·Leukemia & Lymphoma·B J Chen
Oct 3, 2002·Nature Reviews. Cancer·James E Darnell
Feb 7, 2003·Current Cancer Drug Targets·R Z YusufM V Seiden
Mar 15, 2003·Nature Reviews. Cancer·Kristine Novak
Jul 2, 2003·Nature Reviews. Cancer·Roshan Agarwal, Stan B Kaye
Nov 13, 2004·Cell Cycle·Mikhail V Blagosklonny
Nov 9, 2005·International Immunopharmacology·Ru ZhouJian-Ping Zuo
Nov 9, 2005·International Immunopharmacology·Wei TangJian-ping Zuo
Mar 30, 2006·Transplantation·Wei TangJian-ping Zuo
May 23, 2006·Journal of Neuroimmunology·Yun-Feng FuJian-Ping Zuo
Jun 29, 2006·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·T TuranM F Kose
Mar 23, 2007·Acta Pharmacologica Sinica·Yong-xin RenJian-ping Zuo
Apr 6, 2007·Biological & Pharmaceutical Bulletin·Feng ShaoJiye A
Aug 21, 2009·Nature Reviews. Cancer·Mark B MeadsWilliam S Dalton
Oct 20, 2010·Drug and Chemical Toxicology·Jing LiuLuyong Zhang
Feb 1, 2011·Nature Chemical Biology·Denis V TitovJun O Liu
Oct 11, 2011·Cancer Letters·Hongbing ZhaoLiguang Lou
Citations
Feb 10, 2016·Frontiers in Pharmacology·Nima SamieRaja E R Aziddin
Mar 29, 2016·PeerJ·Nima SamieBatoul Sadat Haerian
Jul 3, 2013·Cancer Letters·Quanren WangLiguang Lou
Apr 17, 2014·TheScientificWorldJournal·Maryam HajrezaieMahmood Ameen Abdulla
Jun 12, 2016·Journal of Pharmacological Sciences·Yanke ChenJia Jia
Mar 15, 2015·Scientific Reports·Maryam HajrezaieMahmood Ameen Abdulla
Apr 14, 2016·Scientific Reports·Nima SamieRaja Elina Raja Azudin
Jan 27, 2018·International Journal of Molecular Sciences·Danping FanXiaojuan He
Dec 7, 2017·Frontiers in Pharmacology·Cunzhi YuJin Ren
Aug 5, 2018·Cancer Science·Lei WangLiguang Lou
Jan 22, 2019·Cancer Science·Lei WangLiguang Lou
Mar 2, 2018·Frontiers in Pharmacology·Shao-Ru ChenYing Wang
Nov 14, 2019·Chinese Medicine·Hua LuoYitao Wang
Jun 24, 2020·Chemical Biology & Drug Design·He Zhang, Gongxi Lu
Jan 7, 2016·Toxicology Research·Xinming QiJin Ren
Feb 23, 2020·Nature Communications·Lichan TuWei Gao
Jun 24, 2020·British Journal of Cancer·Lei WangLiguang Lou
Nov 5, 2020·Natural Product Reports·Lu TongJun O Liu
Oct 22, 2020·IScience·Emmanuel DatanJun O Liu
Jul 5, 2019·Current Stem Cell Research & Therapy·Gaole He, Rui Ma
Mar 4, 2021·Thoracic Cancer·Mi ZhangLiguang Lou
Mar 6, 2021·Frontiers in Immunology·Xinpeng ZhouDongyi He