Abstract
One of the recently developed polyamine (PA) analogues, N 1 ,N11-diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to induce autophagy has been established. Unfolded protein responses and starvation of amino acids are known to trigger autophagy. As yet, however, the molecular mechanism underlying PA deficiency-induced autophagy is not fully clarified. Here, we aimed to determine the apoptotic effect of DENSpm after autophagy inhibition by 3-methyladenine (3-MA) or siRNA-mediated Beclin-1 silencing in colon cancer cells. The apoptotic effects of DENSpm after 3-MA treatment or Beclin-1 silencing were determined by PI and AnnexinV/PI staining in conjunction with flow cytometry. Intracellular PA levels were measured by HPLC, whereas autophagy and the expression profiles of PA key players were determined in HCT116, SW480 and HT29 colon cancer cells by Western blotting. We found that DENSpm-induced autophagy was inhibited by 3-MA treatment and Beclin-1 silencing, and that apoptotic cell death was increased by PA depletion and spermidine/spermine N1-acetyltransferase (SSAT) upregulation. We also found that autophagy inhibition led to DEN...Continue Reading
References
Oct 1, 1993·The Journal of Urology·B K ChangG Wang
Oct 1, 1993·Journal of Medicinal Chemistry·N H SaabP M Woster
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·H C HaR A Casero
Apr 29, 1998·Cancer Chemotherapy and Pharmacology·G P ZagajaM E Dolan
Mar 25, 2000·Endocrine-related Cancer·N E DavidsonR A Casero
May 18, 2000·Biochemical and Biophysical Research Communications·K Igarashi, K Kashiwagi
Jul 11, 2000·The Journal of Biological Chemistry·D E McCloskey, A E Pegg
Aug 22, 2000·The Prostate·R G SchipperA A Verhofstad
Feb 16, 2002·European Journal of Biochemistry·Cecilia HegardtStina M Oredsson
Aug 7, 2003·Oncogene·Ying ChenCarl W Porter
Sep 19, 2003·The Biochemical Journal·Heather M WallaceAlun Hughes
Nov 18, 2004·The Journal of Biological Chemistry·Woonyoung ChoiStanley R Hamilton
Mar 17, 2006·Cancer Research·Sophie Pattingre, Beth Levine
Jan 24, 2007·Molecular Cancer Therapeutics·Wendy L AllenPatrick G Johnston
Mar 21, 2007·Biochemical Society Transactions·S M OredssonE Söderstjerna
Oct 3, 2007·Nature Cell Biology·Zhiping Xie, Daniel J Klionsky
Sep 25, 2008·Biochemical Pharmacology·Ella KimWolfgang Deppert
Sep 27, 2008·Cell Cycle·Eugenia MorselliGuido Kroemer
Jul 31, 2009·Oncogene·S Sinha, B Levine
Sep 4, 2009·Cancer Chemotherapy and Pharmacology·Allison Pledgie-TracyNancy E Davidson
Oct 6, 2009·Current Topics in Microbiology and Immunology·Zhifen Yang, Daniel J Klionsky
Oct 6, 2009·Current Topics in Microbiology and Immunology·Noboru Mizushima
Oct 15, 2014·Amino Acids·Ajda Çoker-GürkanNarçin Palavan-Unsal
Nov 25, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zeynep AkyolNarçin Palavan-Ünsal
Sep 21, 2017·Cellular Oncology (Dordrecht)·Worapong KhaodeeRatchada Cressey
Sep 25, 2017·Cellular Oncology (Dordrecht)·Sarita DasChanakya Nath Kundu
Citations
Nov 18, 2018·Molecular Oncology·Liang ShiJianjun Liu
Jan 16, 2019·Cellular Oncology (Dordrecht)·Safieh Ebrahimi, Seyed Isaac Hashemy
Feb 13, 2019·Cancer·Shuo DengAnupam Bishayee
Apr 12, 2019·Medicinal Research Reviews·Xin SunJianbin Zhang
Jul 28, 2020·Carcinogenesis·Takahiro HamoyaMichihiro Mutoh
Oct 12, 2018·Medicinal Research Reviews·Hendrik FolkertsValerie R Wiersma