Abstract
Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers.
References
Dec 7, 1995·Nature·D M Reese
May 2, 1996·The New England Journal of Medicine·G S OmennS Hammar
Jul 29, 1998·Chemico-biological Interactions·P CalvertP J O'Dwyer
Mar 7, 2006·Critical Reviews in Clinical Laboratory Sciences·José M EstrelaElena Obrador
May 27, 2006·Science·Harold Varmus
Jul 11, 2006·The Journal of Chemical Physics·C-R WangQ-B Lu
Jul 19, 2006·Biochemistry·Lei ZhangMarie H Hanigan
May 4, 2007·Journal of Medicinal Chemistry·Q-B Lu
Jun 15, 2007·Molecular Pharmaceutics·Q-B LuC-R Wang
Oct 23, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Charity Mosley-ForemanHongtao Yu
Feb 28, 2009·Molecular Pain·Lauren E TaAnthony J Windebank
Jul 29, 2009·Journal of the American Chemical Society·Chun-Rong WangQing-Bin Lu
Sep 12, 2009·Angewandte Chemie·Janina KopyraEugen Illenberger
Oct 5, 2010·Journal of the American Chemical Society·Chun-Rong Wang, Qing-Bin Lu
Mar 26, 2011·Science·Bruce Alberts
May 12, 2011·Journal of Molecular Modeling·Janina Kuduk-JaworskaJerzy J Jański
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jenny NguyenQing-Bin Lu
Jun 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ting LuoQing-Bin Lu
Sep 21, 2012·Molecular Cancer·Angela CoxonAnthony Polverino
Jan 11, 2013·Open Biology·Jim Watson
Jun 15, 2013·Oxidative Medicine and Cellular Longevity·Nicola TraversoCinzia Domenicotti
Nov 10, 2013·Scientific Reports·Linda Y LuQing-Bin Lu
Citations
Aug 20, 2015·EBioMedicine·A Neesse, E Hessmann
Aug 3, 2016·Angewandte Chemie·Jenny RackwitzIlko Bald
May 20, 2017·The Journal of Physical Chemistry. B·Robin SchürmannIlko Bald
Feb 8, 2018·Macromolecular Bioscience·Susan OliverCyrille Boyer
Jun 18, 2020·Cells·Qing-Bin Lu
Jun 12, 2019·Cells·Robert G GoetzeAlbrecht Neesse
Feb 28, 2016·Molecular Cancer Therapeutics·Chun-Rong WangQing-Bin Lu
Jan 14, 2021·Scientific Reports·Qinrong Zhang, Qing-Bin Lu