Resveratrol augments ER stress and the cytotoxic effects of glycolytic inhibition in neuroblastoma by downregulating Akt in a mechanism independent of SIRT1

Experimental & Molecular Medicine
Regina M GrahamSteven Vanni

Abstract

Cancer cells typically display increased rates of aerobic glycolysis that are correlated with tumor aggressiveness and a poor prognosis. Targeting the glycolytic pathway has emerged as an attractive therapeutic route mainly because it should spare normal cells. Here, we evaluate the effects of combining the inhibition of glycolysis with application of the polyphenolic compound resveratrol (RSV) in neuroblastoma (NB) cancer cell lines. Inhibiting glycolysis with 2-deoxy-D-glucose (2-DG) significantly reduced NB cell viability and was associated with increased endoplasmic reticulum (ER) stress and Akt activity. Administration of 2-DG increased the expression of the ER molecular chaperones GRP78 and GRP94, the prodeath protein C/EBP homology protein (CHOP) and the phosphorylation of Akt at S473, T450 and T308. Combined treatment with both RSV and 2-DG reduced GRP78, GRP94 and Akt phosphorylation but increased CHOP and NB cell death when compared with the administration of 2-DG alone. The selective inhibition of Akt activity also decreased 2-DG-induced GRP78 and GRP94 expression and increased CHOP expression, suggesting that Akt can modulate ER stress. Protein phosphatase 1α (PP1α) was activated by RSV, as indicated by a reduction ...Continue Reading

References

Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y G KwonA C Nairn
May 19, 2006·Cancer Research·Robert A GatenbyRobert J Gillies
Aug 8, 2006·Oncogene·H PelicanoP Huang
Dec 13, 2006·Cancer Metastasis Reviews·Tasnim Ara, Yves A DeClerck
Mar 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brenda J WeigelPeter C Adamson
Dec 2, 2008·Nature Reviews. Drug Discovery·Inki KimJohn C Reed
Jun 11, 2009·Archives of Biochemistry and Biophysics·Mohammad AtharArianna L Kim
Jul 4, 2009·The Journal of Biological Chemistry·Diansheng ZhongWei Zhou
Dec 17, 2009·Journal of Cancer Research and Therapeutics·Seema GuptaB S Dwarakanath
Dec 17, 2009·Journal of Cancer Research and Therapeutics·B S DwarakanathViney Jain
Dec 17, 2009·Journal of Cancer Research and Therapeutics·B S Dwarakanath
Dec 24, 2009·Diabetes·Agueda González-RodríguezAngela M Valverde
Jun 10, 2010·The Journal of Clinical Investigation·Iris EkeNils Cordes
Oct 23, 2010·Molecular Cell·Marcia C Haigis, Bruce A Yankner
Oct 26, 2010·Oncogene·N El MjiyadC Muñoz-Pinedo
Oct 26, 2010·Neurochemical Research·Javier G PizarroAntoni Camins
Nov 10, 2010·PloS One·Jaime R MerchanTheodore J Lampidis
Feb 23, 2011·Cancer Immunology, Immunotherapy : CII·Brenda L SotoPaul M Sondel
Sep 29, 2011·Biochemical and Biophysical Research Communications·Dong-Ho YoonSung-Jo Kim
Apr 12, 2012·Investigative Ophthalmology & Visual Science·Chuanzhou LiLing Zheng
May 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Katherine K MatthayAlice L Yu
Jun 14, 2012·Molecular Cancer Research : MCR·Joanna DeSalvoJulio C Barredo
Jul 21, 2012·Journal of Pediatric Surgery·Kohei MatsushitaMasato Kusunoki
Nov 3, 2012·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Md Ataur RahmanSung-Oh Huh
Nov 16, 2012·Pediatric Radiology·Wolfgang Peter MuellerThomas Pfluger
Jan 15, 2013·International Journal of Molecular Medicine·Yasuko Kitagishi, Satoru Matsuda
Mar 28, 2013·Current Pharmaceutical Design·Mercè PallàsCoral Sanfeliu
Jul 17, 2013·Annals of the New York Academy of Sciences·Andreas GescherKaren Brown

❮ Previous
Next ❯

Citations

Sep 2, 2018·Journal of Cellular Physiology·Sireesh DornadulaRamkumar K Mohanram
Apr 22, 2019·FEBS Open Bio·Vladana DomazetovicMaria Teresa Vincenzini
Sep 14, 2020·Reviews in the Neurosciences·Kamil LeisPrzemysław Gałązka
Aug 29, 2020·Oxidative Medicine and Cellular Longevity·Maura CalvaniClaudio Favre
May 11, 2018·Antioxidants & Redox Signaling·Petr Heneberg
Aug 22, 2018·International Journal of Molecular Sciences·Fatima MaqoudDomenico Tricarico
Oct 30, 2018·Journal of Cellular and Molecular Medicine·Katarzyna KornickaKrzysztof Marycz
Feb 23, 2019·International Journal of Molecular Sciences·Youngjin HanYong Sang Song
Jan 13, 2021·Cancers·Aranka BrockmuellerMehdi Shakibaei
Feb 19, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Daniela Correia da SilvaDavid M Pereira
Dec 15, 2016·Journal of Agricultural and Food Chemistry·Haili WuZhuoyu Li

❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding
xenograft
PCR
Assay
protein
electrophoresis
immunoprecipitation
glycosylation
pulldown

Software Mentioned

Image J

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.