Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells.

Carcinogenesis
Gayathri ChadalapakaStephen Safe

Abstract

Celastrol (CSL) is a naturally occurring triterpenoid acid that exhibits anticancer activity, and in KU7 and 253JB-V bladder cells, CSL induced apoptosis, inhibited growth, colony formation and migration and CSL decreased bladder tumor growth in vivo. CSL also decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and several Sp-regulated genes/proteins including vascular endothelial growth factor, survivin and cyclin D1 and fibroblast growth factor receptor-3, a potential drug target for bladder cancer therapy, has now been characterized as an Sp-regulated gene downregulated by CSL. The mechanism of Sp downregulation by CSL was cell context-dependent due to activation of proteosome-dependent (KU7) and -independent (253JB-V) pathways. In 253JB-V cells, CSL induced reactive oxygen species (ROS) and inhibitors of ROS blocked CSL-induced growth inhibition and repression of Sp1, Sp3 and Sp4. This response was due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of miR-27a and miR-20a/17-5p, respectively, which regulate expression of these transcriptional repressors. Thus, the anticancer activity of CSL in 253JB-V cells is due to induction of ROS and ROS-mediated induction of Sp ...Continue Reading

References

Jun 12, 2002·Current Treatment Options in Oncology·R Dreicer
Sep 19, 2002·The Journal of Pathology·Bas W G van RhijnTheo H van der Kwast
Oct 2, 2003·Bioscience, Biotechnology, and Biochemistry·Masahiro NagaseNobuo Sakato
Aug 25, 2004·Cancer Cell·Colin P N DinneyBogdan Czerniak
Sep 17, 2004·The EMBO Journal·Yoontae LeeV Narry Kim
Jun 22, 2006·Journal of the National Cancer Institute·Maen AbdelrahimStephen Safe
Dec 1, 2006·The Journal of Biological Chemistry·Keith WoodsScott M Hammond
Nov 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sabiha AbbasZe'ev A Ronai
Jan 19, 2008·Molecular Cancer Therapeutics·Tao ZhangDuxin Sun
Jul 3, 2008·Cancer Research·Gayathri ChadalapakaStephen Safe
Apr 10, 2009·European Journal of Pharmacology·Youngmi KimDooil Jeoung
Apr 22, 2009·The Journal of Clinical Investigation·Jing QingAvi Ashkenazi
Oct 28, 2009·The Journal of Biological Chemistry·Tao ZhangDuxin Sun
Apr 22, 2010·Molecular Cancer Research : MCR·Gayathri ChadalapakaStephen Safe
Jul 9, 2010·CA: a Cancer Journal for Clinicians·Ahmedin JemalElizabeth Ward

❮ Previous
Next ❯

Citations

Jul 31, 2013·Archives of Biochemistry and Biophysics·Jin Boo JeongSeong-Ho Lee
May 6, 2014·Expert Opinion on Therapeutic Targets·Stephen SafeIndira Jutooru
Apr 8, 2014·Genes, Chromosomes & Cancer·Vera RiehmerUNKNOWN German Glioma Network
Jun 15, 2013·Journal of Cellular Physiology·Shailendra Kapoor
Nov 5, 2016·Phytotherapy Research : PTR·Stephen Safe, Ravi Kasiappan
Dec 23, 2017·Biological Chemistry·Stephen SafeKeshav Karki
Apr 16, 2014·Molecular and Cellular Biology·Indira JutooruStephen Safe
Feb 20, 2018·Molecular Cancer·Khushwant S BhullarH P Vasantha Rupasinghe
Apr 21, 2019·Antioxidants·Melina MitsiogianniMihalis I Panayiotidis
Aug 18, 2018·Molecular Pharmacology·Keshav KarkiStephen Safe
Jun 20, 2020·Pharmacological Reviews·Tae Jin LeeHolger K Eltzschig
Mar 17, 2018·Cancer Prevention Research·Stephen SafeErik Hedrick
Jan 30, 2015·Cancer Prevention Research·Stephen Safe
Oct 20, 2019·Journal of Molecular Biology·Amelia J HodgesBethany A Buck-Koehntop
Dec 29, 2020·Frontiers in Pharmacology·Jinfeng ShiChaomei Fu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

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