Abstract
The flavonoid quercetin exhibits significant anticancer activities with few side effects. In the current study, we characterized TL-2-8, a quercetin derivative, as a novel anticancer agent in vitro and in vivo. Cell proliferation and viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay, respectively. Cell death was examined using PI staining or a TUNEL assay. Mitophagy was determined by measuring autophagic flux and by confocal imaging. Protein expression was examined by Western blotting. We found that TL-2-8 selectively inhibited the proliferation and decreased the viability of various cancer cells (the anti-proliferation IC50 values in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells at 72 h were 8.28, 8.56, and 9.58 μmol/L, respectively), and it displayed only slight cytotoxicity against normal MCF-10A and HEK-293 cells. In MDA-MB-231 and MDA-MB-468 breast cancer cells, TL-2-8 treatment induced the degradation of multiple Hsp90 client proteins without inducing Hsp70. TL-2-8 (3, 6, 12 μmol/L) dose-dependently inhibited the expression of AHA1, an activator of Hsp90 ATPase, and decreased Hsp90-AHA1 complex formation, leading to decreased Hsp90 chaperone function and reduced polo-like kinase 1 (PLK1) si...Continue Reading
References
May 19, 1997·The Journal of Cell Biology·F A AgarraberesJ F Dice
Jun 1, 1996·Cell Stress & Chaperones·F Ritossa
Sep 6, 2000·Nature·Y TanakaP Saftig
Aug 17, 2004·European Journal of Nutrition·Marjan J van ErkBen van Ommen
Sep 22, 2005·Nature Reviews. Cancer·Luke Whitesell, Susan L Lindquist
Nov 30, 2007·Current Medicinal Chemistry·Celine DidelotCarmen Garrido
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
Feb 19, 2008·Cancer Research·Joanna L HolmesPaul Workman
May 10, 2008·Cancer Letters·Akira MurakamiJunji Terao
Jun 19, 2008·Cancer Research·Yonghua YangKapil Bhalla
Jul 3, 2008·Journal of Agricultural and Food Chemistry·O Benavente-García, J Castillo
Jul 23, 2008·Molecular and Cellular Biology·Urmi BandyopadhyayAna Maria Cuervo
Apr 14, 2009·Gastroenterology·Franco FortunatoJens Werner
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Eloisi Caldas-LopesGabriela Chiosis
Jul 24, 2010·Nature Reviews. Cancer·Jane TrepelLen Neckers
Aug 23, 2011·Molecular Cell·Joung Hyuck JooMondira Kundu
Dec 21, 2012·Scientific Reports·Kahori Shiba-FukushimaNobutaka Hattori
Apr 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yonghua YangKapil N Bhalla
Apr 27, 2013·Science·Yun Chen, Gerald W Dorn
Jan 1, 2014·Nutrition and Cancer·Katrin Sak
Apr 23, 2014·The Journal of Cell Biology·Lesley A KaneRichard J Youle
Oct 7, 2014·Molecular Cell·Alban OrdureauJ Wade Harper
Apr 5, 2015·Carcinogenesis·Joo Ae KimDong Cho Han
Aug 13, 2015·Current Medicinal Chemistry·Ana Filipa BritoMaria Filomena Botelho
Sep 22, 2015·Molecular Cell·Seung Baek LeeZhenkun Lou
Oct 25, 2011·Pharmaceuticals·Peter W Piper, Stefan H Millson
Citations
Sep 7, 2018·Journal of Cellular Biochemistry·Ammad Ahmad FarooqiBaojun Xu
Nov 10, 2020·Acta Pharmaceutica Sinica. B·Lei WangQidong You
May 1, 2021·Cancers·Preethi VetrivelGon Sup Kim
Jun 12, 2021·Bioengineered·Shan MaoJi Li
Jul 6, 2021·Acta Pharmaceutica Sinica. B·Michael A Serwetnyk, Brian S J Blagg
Aug 10, 2021·Frontiers in Pharmacology·Zhonghua FuZhenfang Xiong