AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms

Biochemical and Biophysical Research Communications
Xiaoqin XiangZhijun Luo

Abstract

Prostate cancer cells require high rates of de novo fatty acid synthesis and protein synthesis for their rapid growth. We report here that the growth of these cells is markedly diminished by incubation with activators of AMP-activated protein kinase (AMPK), a fuel-sensing enzyme that has been shown to diminish both of these processes in intact tissues. Inhibition of cell growth was observed when AMPK was activated by either 5-aminoimidazole-4-carboxamide riboside (AICAR) or the thiazolidinedione rosiglitazone. Thus, a 90% inhibition of the growth of androgen-independent (DU145, PC3) and androgen-sensitive (LNCaP) cells was achieved after 4 days of exposure to one or both of these agents. Where studied, this was associated with a decrease in the concentration of malonyl CoA, an intermediate of de novo fatty acid synthesis, and an increase in expression of the cell cycle inhibitor p21. In addition, AICAR inhibited two key enzymes involved in protein synthesis, mTOR and p70S6K, and blocked the ability of the androgen R1881 to increase cell growth and the expression of two enzymes for de novo fatty acid synthesis, acetyl CoA carboxylase and fatty acid synthase, in the LNCaP cells. The results suggest that AMPK is a potential target...Continue Reading

References

Jun 1, 1997·European Journal of Biochemistry·D G Hardie, D Carling
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·J V SwinnenG Verhoeven
Sep 23, 1998·Molecular Medicine Today·J Young, S Povey
Sep 27, 2000·International Journal of Cancer. Journal International Du Cancer·J V SwinnenG Verhoeven
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·J B WelshG M Hampton
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·M S NeshatC L Sawyers
Feb 22, 2002·International Journal of Cancer. Journal International Du Cancer·Johannes V SwinnenGuido Verhoeven
Mar 29, 2002·The Prostate·Xu-Bao ShiRalph W deVere White
Dec 24, 2002·Prostate Cancer and Prostatic Diseases·T J MaatmanK F Shockley
Jan 28, 2003·Biochemical Society Transactions·B E KempL A Witters
Jun 28, 2003·FEBS Letters·D Grahame HardieEmma R Hudson
Jun 28, 2003·FEBS Letters·Jérôme BoudeauDario R Alessi
Aug 15, 2003·International Journal of Cancer. Journal International Du Cancer·Koen BrusselmansJohannes V Swinnen
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Dec 23, 2003·Journal of Cellular Biochemistry·Antonella BaronMassimo Loda
Jan 20, 2004·Trends in Biochemical Sciences·Yong LiKun-Liang Guan
Feb 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Reuben J ShawLewis C Cantley
Mar 26, 2009·Journal of the National Cancer Institute·Toshiro MigitaMassimo Loda

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Citations

Jul 27, 2007·Cell Biochemistry and Biophysics·William W Winder, David M Thomson
Sep 18, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·F P Kuhajda
Aug 22, 2008·The Journal of Biological Chemistry·Cong CaoYinsheng Wan
Mar 19, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·X-X HeS-C J Yeung
Dec 27, 2011·Carcinogenesis·Vaqar Mustafa AdhamiHasan Mukhtar
Aug 2, 2006·Annual Review of Pharmacology and Toxicology·D Grahame Hardie
Apr 29, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giorgia ZadraMassimo Loda
Apr 18, 2009·Molecular Cancer Therapeutics·Hyeon Ung ParkSean P Collins
Jan 10, 2012·Biological & Pharmaceutical Bulletin·Seog Hyeon YounEil Sung Chang
Oct 26, 2013·Endocrine-related Cancer·Hyun-Seuk Moon, Christos S Mantzoros
Dec 15, 2010·Future Oncology·Hany A OmarChing-Shih Chen
Dec 6, 2012·ISRN Oncology·Vajihe IzadiLeila Azadbakht
May 2, 2012·Advances in Urology·Jennifer H GunterColleen C Nelson
Jan 5, 2013·Biochimica Et Biophysica Acta·S E KorsseW van Veelen
Feb 15, 2013·The Journal of Biological Chemistry·Ethan PoteetShao-Hua Yang
Sep 23, 2014·International Journal of Molecular Sciences·Ren-You Gan, Hua-Bin Li
Aug 9, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stefano D'ErricoGennaro Piccialli
Nov 1, 2007·Expert Opinion on Investigational Drugs·Steven J KridelCharles W Pemble
Oct 9, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Olga ScudieroGennaro Piccialli
Apr 7, 2010·Expert Opinion on Investigational Drugs·Eric Van Den NesteFrançoise Bontemps
Nov 12, 2014·Annual Review of Medicine·Daniel R Morales, Andrew D Morris
Jan 30, 2013·Pharmacology & Therapeutics·Santiago Diaz-MoralliMarta Cascante
Apr 15, 2006·The Journal of Physiology·Hiroyuki MotoshimaEiichi Araki
Jul 18, 2012·Molecular and Cellular Endocrinology·Kristy A BrownEvan R Simpson

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