Abstract
5'-Nitro-indirubinoxime (5'-NIO) is a new derivative of indirubin that exhibits anti-cancer activity in a variety of human cancer cells. However, its mechanism has not been fully clarified. Human salivary gland adenocarcinoma (SGT) cells were used in this study. Western blot and RT-PCR analyses were performed to determine cellular Notch levels. The cell cycle stage and level of apoptosis were analyzed using flow cytometry analysis. 5'-NIO significantly inhibited the mRNA levels of Notch-1 and Notch-3 and their ligands (Delta1, 2, 3, and Jagged-2) in SGT cells. Immunocytochemistry analysis showed that 5'-NIO specifically decreased the level of Notch-1 in the nucleus. In addition, 5'-NIO induced G1 cell cycle arrest by reducing levels of CDK4 and CDK6 in SGT cells. Using flow cytometry and immunoblotting analysis, we found that 5'-NIO induces apoptosis following the secretion of cytochrome c and the activation of caspase-3 and caspase-7. Intracellular Notch-1 overexpression led to a decrease in G1 phase arrest and an inhibition of 5'-NIO-induced apoptosis. These observations suggest that 5'-NIO induces cell cycle arrest and apoptosis by down-regulating Notch-1 signaling. This study identifies a new mechanism of 5'-NIO-mediated an...Continue Reading
References
Apr 30, 1999·Science·S Artavanis-TsakonasR J Lake
Aug 17, 2000·Journal of the National Cancer Institute·T P DangD P Carbone
Jul 6, 2001·Oncogene·E DamiensL Meijer
Jan 28, 2003·Journal of Cellular Physiology·Tatsuya IsoYasuo Hamamori
Apr 11, 2003·Leukemia & Lymphoma·Zhijian XiaoLingsheng Qian
Jul 5, 2003·Cancer Cell·Yoshiharu MiyamotoSteven D Leach
Feb 26, 2004·Oncogene·Daniel E ToddSimon J Cook
Apr 20, 2004·Journal of Cellular Physiology·Mei-Shiang JangLucio Miele
Aug 4, 2004·Seminars in Cancer Biology·Emil M HanssonGavin Chapman
Sep 1, 2004·Neuroscience Letters·Yuanbin XieMingtao Li
Dec 16, 2004·International Journal of Clinical Pharmacology and Therapeutics·K H MerzG Eisenbrand
Apr 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sangkil NamRichard Jove
Jul 5, 2005·Bioorganic & Medicinal Chemistry Letters·Jong-Won LeeSang Kook Lee
May 3, 2006·Cancer Research·Sathish Kumar MungamuriKumaravel Somasundaram
Jun 17, 2006·Cancer Research·Joon T ParkTian-Li Wang
Jan 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Soo-A KimJung-Hoon Yoon
May 30, 2007·Oncogene·Y ZhenA Wiedłocha
Sep 8, 2007·Cellular Signalling·Tao WangDorothy Trump
Sep 15, 2007·Progress in Biophysics and Molecular Biology·Tao WangDorothy Trump
Oct 18, 2008·Cancer Letters·Soo-A KimSang-Gun Ahn
Nov 26, 2008·Breast Cancer Research : BCR·Connie W LeeDario C Altieri
Citations
Feb 15, 2013·PloS One·Jian LiuZhenhe Suo
Nov 26, 2011·Cancer Letters·Hyo-Eun YoonSang-Gun Ahn
Oct 27, 2015·Apoptosis : an International Journal on Programmed Cell Death·Chong ZengFeiyue Xing
Apr 6, 2011·Cancer Letters·Soo-A KimSang-Gun Ahn
Feb 11, 2011·Journal of Cellular Biochemistry·Shengkai LiaoZhiwei Wang
Oct 13, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Tina BlaževićPavel Uhrin
Jun 25, 2013·Cancer Biology & Therapy·Karina KristoffersenMarie-Thérése Stockhausen
Mar 20, 2015·Oncology Letters·Ling WangXin Wang
Mar 13, 2014·PloS One·John C MorrisDonald P Lawrence
Jan 28, 2020·Archiv der Pharmazie·Ya-Zhou ZhangZhi Xu
Mar 2, 2013·Oncology Reports·Wei ChenSenlin Zhang
Mar 8, 2013·Oncology Reports·Ming-Yang LeeJing-Jing Chuang
Apr 7, 2010·Journal of Medicinal Chemistry·Soo-Jeong ChoiYong-Chul Kim
Jun 24, 2021·European Journal of Medicinal Chemistry·Hezhen WangYongzheng Chen