Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress.

Cells
Fernanda AntunesSoraya Soubhi Smaili

Abstract

Skin melanoma is one of the most aggressive and difficult-to-treat human malignancies, characterized by poor survival rates, thus requiring urgent novel therapeutic approaches. Although metabolic reprogramming has represented so far, a cancer hallmark, accumulating data indicate a high plasticity of cancer cells in modulating cellular metabolism to adapt to a heterogeneous and continuously changing microenvironment, suggesting a novel therapeutic approach for dietary manipulation in cancer therapy. To this aim, we exposed melanoma cells to combined nutrient-restriction/sorafenib. Results indicate that cell death was efficiently induced, with apoptosis representing the prominent feature. In contrast, autophagy was blocked in the final stage by this treatment, similarly to chloroquine, which also enhanced melanoma cell sensitization to combined treatment. Energy stress was evidenced by associated treatment with mitochondrial dysfunction and glycolysis impairment, suggesting metabolic stress determining melanoma cell death. A reduction of tumor growth after cycles of intermittent fasting together with sorafenib treatment was also observed in vivo, reinforcing that the nutrient shortage can potentiate anti-melanoma therapy. Our fin...Continue Reading

References

Mar 27, 2007·Nuclear Medicine and Biology·William C EckelmanJohn F Valliant
Oct 28, 2009·International Journal of Cancer. Journal International Du Cancer·Wilhelm G DirksHiroshi Mizusawa
Dec 17, 2009·Journal of Cancer Research and Therapeutics·B S DwarakanathViney Jain
Dec 17, 2009·Journal of Cancer Research and Therapeutics·Abdullah FarooqueB S Dwarakanath
Mar 27, 2010·Revista da Associação Médica Brasileira·Sueli Blanes DamyLuiz Francisco Poli de Figueiredo
Apr 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Frank WeinbergNavdeep S Chandel
Jan 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jane L ArmstrongPenny E Lovat
Apr 22, 2011·Nature Reviews. Cancer·Willem H KoppenolChi V Dang
Aug 16, 2011·Clinical & Experimental Metastasis·Joseph L SottnikDouglas H Thamm
Aug 23, 2011·International Journal of Cancer. Journal International Du Cancer·Satoshi ShimizuNorio Hayashi
Jan 25, 2012·Journal of Proteome Research·Vibeke Hervik BullBernd Thiede
Feb 11, 2012·Science Translational Medicine·Changhan LeeValter D Longo
Mar 24, 2012·Cancer Cell·Patrick S Ward, Craig B Thompson
May 3, 2012·Genes & Development·Chi V Dang
Sep 1, 2012·Science·Richard J Youle, Alexander M van der Bliek
Sep 18, 2012·PloS One·Fernando SafdieValter D Longo
Jul 17, 2013·Seminars in Cancer Biology·Marco CorazzariMauro Piacentini
Aug 22, 2013·Breast Cancer Research and Treatment·Claudia FumarolaMara A Bonelli
Jan 10, 2014·Nature Reviews. Molecular Cell Biology·Guillermo MariñoGuido Kroemer
Jan 21, 2014·Cell Metabolism·Valter D Longo, Mark P Mattson
Jul 20, 2014·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·A Ramírez-LabradaJ Naval
Sep 12, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B EscudierUNKNOWN ESMO Guidelines Working Group
Dec 17, 2014·Developmental Cell·Manuela AntonioliGian Maria Fimia
Jan 27, 2015·Journal of Cell Science·Vittoria PagliariniMarco Corazzari
Jan 27, 2015·Trends in Molecular Medicine·Cecilie Abildgaard, Per Guldberg
Mar 5, 2015·Seminars in Cell & Developmental Biology·Najoua LalaouiPaul G Ekert
Mar 21, 2015·Oncology Research and Treatment·Xiao Dong XuHai Tao Niu
Sep 30, 2015·Oncotarget·Pedram KharazihaTheocharis Panaretakis
Nov 22, 2015·Pharmacological Reviews·Hagir B Suliman, Claude A Piantadosi
Jan 12, 2016·British Journal of Pharmacology·Bhaskar BhattacharyaRichie Soong
Jan 31, 2016·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J A Guadarrama-OrozcoC Lopez-Camarillo
Mar 15, 2016·Cellular and Molecular Neurobiology·Xiangyu LiuYuyuan Dai
May 20, 2016·Molecular Cancer Therapeutics·Zheqiong TanYa Cao

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Citations

Apr 29, 2020·International Journal of Molecular Sciences·Mariusz L Hartman
Mar 14, 2021·Cell Death Discovery·Mara GagliardiMarco Corazzari
Sep 26, 2020·Seminars in Cancer Biology·Mona AlidadiAmirhossein Sahebkar

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Methods Mentioned

BETA
flow cytometry
FACS
confocal microscopy
PCR

Software Mentioned

ZEN lite
[UNK]
ImageJ
Primer
Express
Uvitec Alliance

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