PMID: 23902736Aug 2, 2013Paper

Small molecule-induced mitochondrial disruption directs prostate cancer inhibition via UPR signaling

Oncotarget
Elizabeth Rico-BautistaDieter A Wolf

Abstract

We previously identified SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) as a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony formation in soft agar, and cell death. However, the mechanism of SMIP004-induced cancer cell selective apoptosis remained unknown. Here, we used chemical genomic and proteomic profiling to unravel a SMIP004-induced pro-apoptotic pathway, which initiates with disruption of mitochondrial respiration leading to oxidative stress. This, in turn, activates two pathways, one eliciting cell cycle arrest by rapidly targeting cyclin D1 for proteasomal degradation and driving the transcriptional downregulation of the androgen receptor, and a second pathway that activates pro-apoptotic signaling through MAPK activation downstream of the unfolded protein response (UPR). SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice. Our data suggest that SMIP004, by inducing mitochondrial ROS formation, targets specific sensitivities of prostate cancer cells to redox and bioenergetic imbalances that can ...Continue Reading

References

Oct 1, 1976·Science·P C Nowell
Nov 24, 1995·Science·Z XiaM E Greenberg
Mar 14, 1997·Science·K IraniP J Goldschmidt-Clermont
May 29, 1999·The Journal of Biological Chemistry·A Barrientos, C T Moraes
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·J W BrewerJ A Diehl
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Oct 6, 2000·Medical Hypotheses·Q KongK O Lillehei
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·J W Brewer, J A Diehl
Jan 2, 2004·Nature Medicine·Charlie D ChenCharles L Sawyers
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Matthew D Petroski, Raymond J Deshaies
Dec 7, 2005·Oncogene·L Zhang, C Wang
Mar 30, 2007·Nature·Fumiaki OhtakeShigeaki Kato
Sep 25, 2007·Cell·Nicole L SoliminiStephen J Elledge
Oct 19, 2007·Nucleic Acids Research·John F ReichardAlvaro Puga
Nov 6, 2007·Antioxidants & Redox Signaling·Jyoti D Malhotra, Randal J Kaufman
Aug 30, 2008·Molecular Cancer Therapeutics·Jessica R KirshnerJohn Bertin
Dec 2, 2008·Nature Reviews. Drug Discovery·Inki KimJohn C Reed
Dec 23, 2008·Seminars in Cancer Biology·Vladimir GogvadzeBoris Zhivotovsky
Mar 11, 2009·Methods : a Companion to Methods in Enzymology·Laurence M BrillDieter A Wolf
Apr 11, 2009·Nature·Teresa A SoucySteven P Langston
May 6, 2009·Journal of Cellular Physiology·Jong Kyong Kim, J Alan Diehl
Jun 6, 2009·Antioxidants & Redox Signaling·Georg T Wondrak
Oct 20, 2009·European Journal of Pharmacology·Sandra J M HealyAfshin Samali
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anne LeChi V Dang
Sep 17, 2010·Genes & Development·Michael M Shen, Cory Abate-Shen
Nov 26, 2010·The Journal of Clinical Investigation·Ankur SharmaKaren E Knudsen
Jan 21, 2011·Nature·Jane E Visvader
Jan 22, 2011·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keiko TaguchiMasayuki Yamamoto
Feb 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francois LamoureuxAmina Zoubeidi
Mar 3, 2011·Nature Cell Biology·Ira Tabas, David Ron
May 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Meifan ChenZe'ev A Ronai
Jan 4, 2012·Histopathology·Christopher E BarbieriMark A Rubin

❮ Previous
Next ❯

Citations

Jul 21, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ammad Ahmad FarooqiHsueh-Wei Chang
Oct 23, 2015·Mediators of Inflammation·Claudia GiampietriElio Ziparo
Nov 20, 2018·Expert Opinion on Therapeutic Patents·Xin LiQ Ping Dou
Mar 10, 2018·Cancers·Prashanth K B NageshMurali M Yallapu
Mar 14, 2019·Oxidative Medicine and Cellular Longevity·Anna WalczakIreneusz Majsterek
May 12, 2020·Medicinal Research Reviews·Moges Dessale AsmamawHong-Min Liu
Oct 12, 2018·Carcinogenesis·Jialin XiaoRenee Reams
Jul 28, 2016·Clinical and Translational Medicine·Vicent RibasJosé C Fernández-Checa
Jan 28, 2014·Biochemistry. Biokhimii︠a︡·M Y VyssokikhV P Skulachev
Nov 27, 2014·Oncotarget·Qiao Jing LewSheng-Hao Chao
Jul 28, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuning LinYanfei Wei
Dec 18, 2013·Seminars in Pediatric Neurology·Christos D KatsetosPavel Dráber

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.