Abstract
Heat shock protein 90 (Hsp90) is an attractive therapeutic target. Geldanamycin (GA), the first identified Hsp90 inhibitor, exhibited potent antitumor activity, but possessed significant hepatotoxicity. To overcome the hepatotoxicity derived from the quinone structure of GA, a non-quinone GA derivative 17-demethoxy-reblastatin (17-DR) was obtained from a genetically modified strain of Streptomyces hygroscopicus. In the present study, we examined the anticancer effects of 17-DR on human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, and its underlying mechanisms. The results indicated that 17-DR could concentration-dependently inhibit the proliferation, and decrease the colony formation in HCC cells. It also induced significant apoptosis in HCC cells, which was mediated by mitochondria via a caspase-dependent pathway. The mechanisms involved in 17-DR-induced apoptosis included the downregulation of myeloid cell leukemia-1 (Mcl-1), and upregulation of Bcl-2 antagonist killer 1 (Bak). And the upregulated Bak expression resulted from downregulation of Mcl-1 played an essential role in this process. Taken together, these results indicated that 17-DR possessed potent anticancer effects on HCC cells by inhibiting cell p...Continue Reading
References
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·J G SupkoL Malspeis
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·L WhitesellL M Neckers
Sep 12, 1998·Science·J M Adams, S Cory
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·J C Martinou, D R Green
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Len NeckersTheodor W. Schulte
Sep 26, 2003·Nature·Adeela KamalFrancis J Burrows
Jun 5, 2004·Trends in Molecular Medicine·Adeela KamalFrancis J Burrows
Jun 7, 2005·Cell·Douglas R Green
Apr 4, 2007·Genes & Development·Tsutomu ShimazuMasayori Inouye
Jul 10, 2009·Journal of Virology·Alicia F Pearce, Douglas S Lyles
Jun 10, 2010·Nature Reviews. Molecular Cell Biology·Mikko TaipaleSusan Lindquist
Aug 20, 2011·Expert Opinion on Investigational Drugs·Bridget A QuinnPaul B Fisher
Jan 13, 2012·Journal of Proteomics·Viviane C H da Silva, Carlos H I Ramos
Apr 4, 2012·Oncotarget·Melchiorre CervelloGiuseppe Montalto
Apr 10, 2012·Experimental Cell Research·Emma DeanCaroline Dive
Apr 13, 2012·EMBO Molecular Medicine·Luigi LeanzaIldikò Szabò
Nov 6, 2012·Journal of Microbiology and Biotechnology·Cheng-Zhu WuYoung-Soo Hong
Nov 14, 2012·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Angela Gauthier, Mitchell Ho
Dec 12, 2012·Oncology Reports·Lijuan ZhuoAimin Huang
Jan 22, 2013·Communicative & Integrative Biology·Qiang Liu, Hong-Gang Wang
May 7, 2013·Expert Opinion on Therapeutic Patents·TaeHun KimAe Nim Pae
Mar 25, 2014·Pigment Cell & Melanoma Research·Nethia Mohana-KumaranNikolas K Haass
Apr 8, 2014·Journal of Microbiology and Biotechnology·Qing ZhaoHao Liu
Jun 6, 2014·Clinical Medicine Insights. Oncology·Avegail Flores, Jorge A Marrero
Jul 18, 2014·Cancer Chemotherapy and Pharmacology·Yun ZhengH Phillip Koeffler
Sep 2, 2014·Oncology Reports·Wei ZhangYahui Liu
Oct 15, 2014·European Journal of Medicinal Chemistry·Danqi ChenJingkang Shen
Citations
Jun 22, 2017·Future Medicinal Chemistry·Qingbin CuiPeng Huang
Nov 30, 2018·Molecular Medicine Reports·Li DongRuifang Guo
May 27, 2020·Journal of Cellular Physiology·Masoud Nouri-VaskehBehzad Baradaran
Sep 24, 2016·Journal of Experimental & Clinical Cancer Research : CR·Zhirui ZhangHao Liu
Feb 2, 2018·Oncology Letters·Xueqin ChenShenglin Ma
Mar 7, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ruizhi WangXiaolin Wang
Feb 6, 2016·International Journal of Molecular Medicine·Xin LiuQiuran Xu