Chemopreventive sphingadienes downregulate Wnt signaling via a PP2A/Akt/GSK3β pathway in colon cancer.

Carcinogenesis
Ashok KumarJulie D Saba

Abstract

Sphingadienes (SDs) derived from soy and other natural sphingolipids are cytotoxic to colon cancer cells via an Akt-dependent mechanism and reduce adenoma formation in Apc(Min/+) mice. Wnt signaling is fundamental to colon carcinogenesis and is the basis for spontaneous tumorigenesis in Apc(Min/+) mice and patients with familial adenomatous polyposis. In the present study, we investigated the impact of SDs on Wnt signaling. Oral SD administration reduced levels of active β-catenin and Wnt targets c-Myc and cyclin D1 in Apc(Min/+) mouse intestinal tissues. Colon cancer cells treated with SDs exhibited reduced Wnt transcriptional activity, as well as reduced nuclear β-catenin localization and subsequent reduction in active-β-catenin levels. Further, we observed a decrease in phosphorylated (inactive) GSK3β in SD-treated mice and colon cancer cells. Expression of constitutively active myristoylated-Akt or inactivation of GSK3β using LiCl attenuated SD-mediated inhibition of Wnt transcriptional activity and active-β-catenin levels. SDs exhibited additive effects with inhibitors of the phosphatidylinositol-3-kinase/Akt/mTOR pathway to induce cytotoxicity. Further, a combination regime of SDs and low-dose rapamycin decreased visible ...Continue Reading

References

May 3, 1996·International Journal of Cancer. Journal International Du Cancer·E A SweeneyY Igarashi
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·S RamaswamyW R Sellers
Jun 22, 1999·Molecular and Cellular Biology·X Chen, R Prywes
Jun 22, 1999·Current Opinion in Immunology·M López-Botet, T Bellón
Apr 18, 2000·Journal of Mass Spectrometry : JMS·M C SullardsJ Adams
Aug 26, 2000·Cytokine & Growth Factor Reviews·T Akiyama
Sep 29, 2000·Biochemical Pharmacology·S Zolnierowicz
Nov 1, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·N Barker, H Clevers
Dec 15, 2000·Current Biology : CB·P XiaM A Vadas
Oct 5, 2001·The Journal of Nutrition·C C AbnetS M Dawsey
Dec 26, 2001·EMBO Reports·Frank J T StaalHans C Clevers
Apr 27, 2002·Experimental Biology and Medicine·Eun Hyun Ahn, Joseph J Schroeder
Apr 18, 2003·Current Biology : CB·Michael T VeemanRandall T Moon
Jan 27, 2004·The Journal of Pharmacology and Experimental Therapeutics·Amanda P StruckhoffBarbara S Beckman
Oct 28, 2005·Journal of Lipid Research·Ake Nilsson, Rui-Dong Duan
Nov 1, 2005·Cell Cycle·Serge Y FuchsToshinari Minamoto
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Irwin I SingerElizabeth J Quackenbush
Dec 2, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Toshihiko KawamoriDaohong Zhou
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Mar 8, 2006·Experimental & Molecular Medicine·Akira KikuchiHideki Yamamoto
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Babak OskouianJulie D Saba
Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·Wim de LauHans Clevers
Jun 15, 2007·Journal of Natural Products·Lie-Ching RowChiu-Ming Chen
Oct 1, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Toshihiko KawamoriLina M Obeid
Oct 24, 2009·The Journal of Biological Chemistry·Ser Sue NgHans Clevers
Mar 10, 2010·Journal of Lipid Research·Tatsuya SugawaraTakashi Hirata
Sep 24, 2010·PloS One·Matthew Lovatt, Marie-José Bijlmakers
Sep 28, 2010·Reviews on Recent Clinical Trials·Aruni S Arachchige Don, X F Steven Zheng
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini

❮ Previous
Next ❯

Citations

Dec 7, 2013·Gastroenterology Research and Practice·Weibo ChenYitao Ding
Oct 28, 2014·The Journal of Clinical Investigation·Emilie DegagnéJulie D Saba
Mar 5, 2013·Archives of Biochemistry and Biophysics·Monika Sakowicz-BurkiewiczTadeusz Pawelczyk
Oct 23, 2012·Chemistry and Physics of Lipids·Hoe-Sup Byun, Robert Bittman
Dec 26, 2015·Journal of Cancer Research and Clinical Oncology·Yu-Sheng ZhangXian-Jun Qu
Sep 12, 2015·The Journal of Nutritional Biochemistry·Zeinab SaadatdoustMohd Rais Mustafa
Dec 15, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mei Guo, Jun Dou
Aug 2, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Ashok Kumar Pandurangan, Norhaizan Mohd Esa
Jan 1, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Ashok Kumar PanduranganSudhandiran Ganapasam
Jan 15, 2014·International Journal of Cancer. Journal International Du Cancer·Wenhao WengYanlei Ma
Sep 13, 2013·Toxicology Mechanisms and Methods·Ashok Kumar PanduranganSudhandiran Ganapasam
Feb 26, 2016·Critical Reviews in Biochemistry and Molecular Biology·Nathan Wlodarchak, Yongna Xing
Jul 10, 2016·Neuromolecular Medicine·Mitchell K P LaiDeron R Herr
Apr 16, 2013·BioMed Research International·Rodolfo IulianoNicola Perrotti
Jul 6, 2017·American Journal of Respiratory Cell and Molecular Biology·Christine U VohwinkelIstván Vadász
Dec 5, 2014·Biological Chemistry·Nigel J Pyne, Richard N Kolesnick
Sep 25, 2020·Lipids·Wajiha Farha Faqar-Uz-ZamanAnja Schwiebs
Jun 12, 2020·Metabolites·Timothy Andrew CouttasAnthony Simon Don
Jul 8, 2017·Cancer Biology & Therapy·E Ramsay CampChristina Voelkel-Johnson
Dec 3, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Ashok Kumar Pandurangan, Norhaizan Mohd Esa
Feb 18, 2014·Human & Experimental Toxicology·A K PanduranganS Ganapasam
Dec 29, 2020·Cellular Signalling·Brenda Wan Shing LamDeron R Herr
Feb 9, 2021·Critical Reviews in Food Science and Nutrition·Li GaoJiaoyan Ren
Oct 27, 2021·Journal of Neurochemistry·Caine C SmithGreg T Sutherland

❮ Previous
Next ❯

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.

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.