Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis.

Cancer Research
Henrik FyrstJulie D Saba

Abstract

Sphingolipid metabolites regulate cell proliferation, migration, and stress responses. Alterations in sphingolipid metabolism have been proposed to contribute to carcinogenesis, cancer progression, and drug resistance. We identified a family of natural sphingolipids called sphingadienes and investigated their effects in colon cancer. We find that sphingadienes induce colon cancer cell death in vitro and prevent intestinal tumorigenesis in vivo. Sphingadienes exert their influence by blocking Akt translocation from the cytosol to the membrane, thereby inhibiting protein translation and promoting apoptosis and autophagy. Sphingadienes are orally available, are slowly metabolized through the sphingolipid degradative pathway, and show limited short-term toxicity. Thus, sphingadienes represent a new class of therapeutic and/or chemopreventive agents that blocks Akt signaling in neoplastic and preneoplastic cells.

References

Feb 1, 1991·Journal of Bioenergetics and Biomembranes·A H Merrill
Feb 1, 1995·Trends in Biochemical Sciences·Y A Hannun, L M Obeid
May 3, 1996·International Journal of Cancer. Journal International Du Cancer·E A SweeneyY Igarashi
Jul 31, 1998·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·W F DoveA R Shoemaker
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·S RamaswamyW R Sellers
Dec 15, 2000·Current Biology : CB·P XiaM A Vadas
Dec 1, 2001·Science·T HlaM J Kluk
May 2, 2002·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·B BerraA Giacosa
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Apr 3, 2003·Lipids·Jian-Wen TanJi-Kai Liu
Nov 1, 2003·Archives of Biochemistry and Biophysics·Lori A LemonnierEva M Schmelz
Dec 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Linnea M BaudhuinYan Xu
Jan 27, 2004·The Journal of Pharmacology and Experimental Therapeutics·Amanda P StruckhoffBarbara S Beckman
Jun 23, 2004·Seminars in Cell & Developmental Biology·Sophie DegrooteGerrit van Meer
Mar 23, 2005·Current Opinion in Cell Biology·James R Woodgett
Jun 14, 2005·Cancer Cell·Yardena SamuelsVictor E Velculescu
Oct 28, 2005·Journal of Lipid Research·Ake Nilsson, Rui-Dong Duan
Nov 17, 2005·Oncogene·Davide Ruggero, Nahum Sonenberg
Sep 19, 2006·Molecular and Cellular Biology·Masataka KohnoTimothy Hla
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Babak OskouianJulie D Saba
Dec 8, 2006·Bioscience, Biotechnology, and Biochemistry·Tatsuya SugawaraTakashi Hirata
Feb 13, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Christopher K MeansJoan Heller Brown
Jun 15, 2007·Cellular and Molecular Life Sciences : CMLS·S Lahiri, A H Futerman
Jun 15, 2007·Journal of Natural Products·Lie-Ching RowChiu-Ming Chen
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Oct 9, 2007·Trends in Biochemical Sciences·Tom CrabbeStephen G Ward
Nov 17, 2007·Genes & Development·Noboru Mizushima
Mar 10, 2009·Biochimica Et Biophysica Acta·Roger H KimSarah Spiegel

❮ Previous
Next ❯

Citations

May 24, 2014·Cell Death & Disease·Y LiL Xiong
Oct 28, 2014·The Journal of Clinical Investigation·Emilie DegagnéJulie D Saba
Jun 19, 2010·Nature Chemical Biology·Henrik Fyrst, Julie D Saba
Oct 23, 2012·Chemistry and Physics of Lipids·Hoe-Sup Byun, Robert Bittman
Jan 11, 2011·Journal of Neurochemistry·Rachel Kraut
Jul 10, 2016·Neuromolecular Medicine·Mitchell K P LaiDeron R Herr
Dec 17, 2015·Journal of Lipid Research·Siddabasave Gowda B GowdaKenji Monde
Jun 20, 2012·International Journal of Molecular Medicine·Evelien RozemaBrigitte Kopp
Dec 22, 2019·The Journal of Biological Chemistry·Gergely KarsaiThorsten Hornemann
Oct 26, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anabel S de la Garza-RodeaJulie D Saba
Sep 14, 2019·American Journal of Respiratory Cell and Molecular Biology·Gayatri GuptaPatrick Geraghty
Dec 5, 2014·Biological Chemistry·Nigel J Pyne, Richard N Kolesnick
Dec 29, 2019·Scientific Reports·Tejia ZhangRandall T Peterson
Jun 12, 2020·Metabolites·Timothy Andrew CouttasAnthony Simon Don
Oct 2, 2013·The Journal of Biological Chemistry·Yuquan XiongTimothy Hla
Aug 6, 2015·Expert Opinion on Therapeutic Targets·Wei-Yi OngAkhlaq A Farooqui
Dec 29, 2020·Cellular Signalling·Brenda Wan Shing LamDeron R Herr
Aug 25, 2019·Progress in Lipid Research·A C CarreiraL C Silva
Dec 4, 2020·Cellular Signalling·Ruijuan XuCungui Mao

❮ 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.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms