TITLE

Inhibition of gamma-secretase induces G2/M arrest and triggers apoptosis in breast cancer cells

AUTHOR(S)
Rasul, S.; Balasubramanian, R.; Filipović, A.; Slade, M. J.; Yagüe, E.; Coombes, R. C.; Filipović, A; Yagüe, E
PUB. DATE
June 2009
SOURCE
British Journal of Cancer;6/16/2009, Vol. 100 Issue 12, p1879
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
Gamma-secretase activity is vital for the transmembrane cleavage of Notch receptors and the subsequent migration of their intracellular domains to the nucleus. Notch overexpression has been associated with breast, colon, cervical and prostate cancers. We tested the effect of three different gamma-secretase inhibitors (GSIs) in breast cancer cells. One inhibitor (GSI1) was lethal to breast cancer cell lines at concentrations of 2 muM and above but had a minimal effect on the non-malignant breast lines. GSI1 was also cytotoxic for a wide variety of cancer cell lines in the NCI60 cell screen. GSI1 treatment resulted in a marked decrease in gamma-secretase activity and downregulation of the Notch signalling pathway with no effects on expression of the gamma-secretase components or ligands. Flow cytometric and western blot analyses indicated that GSI1 induces a G2/M arrest leading to apoptosis, through downregulation of Bcl-2, Bax and Bcl-XL. GSI1 also inhibited proteasome activity. Thus, the gamma-secretase inhibitor GSI1 has a complex mode of action to inhibit breast cancer cell survival and may represent a novel therapy in breast cancer.
ACCESSION #
41335436

 

Related Articles

  • Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Corsetto, Paola A.; Montorfano, Gigliola; Zava, Stefania; Jovenitti, Ilaria E.; Cremona, Andrea; Berra, Bruno; Rizzo, Angela M. // Lipids in Health & Disease;2011, Vol. 10 Issue 1, p73 

    Background: PUFAs are important molecules for membrane order and function; they can modify inflammationinducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive,...

  • Benzo[b]thiophenesulphonamide 1,1-dioxide derivatives inhibit tNOX activity in a redox state-dependent manner. Encío, I; Morr&seacute;, D J; Villar, R; Gil, M J; Martínez-Merino, V // British Journal of Cancer;2/28/2005, Vol. 92 Issue 4, p690 

    Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and...

  • Different BAG-1 isoforms have distinct functions in modulating chemotherapeutic-induced apoptosis in breast cancer cells. Hong-yu LIU; Zhuo-min WANG; Yun BAI; Min WANG; Ying LI; Sen WEI; Qing-hua ZHOU; Jun CHEN // Acta Pharmacologica Sinica;Feb2009, Vol. 30 Issue 2, p235 

    AbstractAim:BAG-1 is a multifunctional anti-apoptotic gene with four isoforms, and different BAG-1 isoforms have different anti-apoptotic functions. In this study, we transfected BAG-1 isoforms into the human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive) to study their...

  • THE BREAST OF ANTICANCER FROM LEAF EXTRACT OF ANNONA MURICATA AGAINTS CELL LINE IN T47D. Suhesti, Tuti Sri; Widiastuti, Retno; Rachmani, Eka Prasasti Nur; Aditiyono // International Journal of Applied Science & Technology;Jan2012, Vol. 2 Issue 1, p157 

    The breast cancer is the second leading cause of death in women after cervical cancer. The soursop (Annona muricata) is a traditional medicinal plant which is empirically by the people of Indonesia are used for anti-inflammatory and anti-tumor. This study aims to determine the cytotoxic effects...

  • Jordanian Ducrosia flabellifolia Inhibits Proliferation of Breast Cancer Cells by Inducing Apoptosis. Talib, Wamidh H.; Issa, Reem A.; Kherissat, Feryal; Mahasneh, Adel M. // British Journal of Medicine & Medical Research;Jul-Sep2013, Vol. 3 Issue 3, p771 

    Aims: to evaluate the potential apoptosis inducing effect of Ducrosia flabellifolia extracts against different cancer cell lines. Methodology: The antiproliferative activity of Ducrosia flabellifolia extracts was tested against three cell lines using MTT assay. The apoptosis induction ability of...

  • Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells. Katherine Liu; Shundong Cang; Yuehua Ma; Jen Wei Chiao // Cancer Cell International;2013, Vol. 13 Issue 1, p1 

    This study examined whether combining paclitaxel (taxol) with a novel epigenetic agent phenethyl isothiocyanate (PEITC) will yield a synergistic effect on inhibiting breast cancer cells. Two drug-resistant breast cancer cell lines, MCF7 and MDA-MB-231, were treated with PEITC and taxol. Cell...

  • Erbin-regulated Sensitivity of MCF-7 Breast Cancer Cells to TRAIL via ErbB2/AKT/NF-κB Pathway. Ning Liu; Jindan Zhang; Jinchun Zhang; Shilian Liu; Yanxin Liu; Dexian Zheng // Journal of Biochemistry;Jun2008, Vol. 143 Issue 6, p793 

    We have reported that Erbin expression was down-regulated in the Jurkat leukaemia T lymphocytes treated with the recombinant soluble tumour necrosis factor-related apoptosis-inducing ligand (rsTRAIL). Herein, we studied the expression and the regulation of Erbin and its binding partner, ErbB2,...

  • Intrinsic Mechanism of Estradiol-Induced Apoptosis in Breast Cancer Cells Resistant to Estrogen Deprivation. Lewis, Joan S.; Meeke, Kathleen; Osipo, Clodia; Ross, Eric A.; Kidawi, Noman; Li, Tianyu; Bell, Eric; Chandel, Navdeep S.; Jordan, V. Craig // JNCI: Journal of the National Cancer Institute;12/7/2005, Vol. 97 Issue 23, p1746 

    Background: We previously developed an estrogen receptor (ER)-positive breast cancer cell line (MCF-7:5C) that is resistant to long-term estrogen deprivation and undergoes rapid and complete apoptosis in the presence of physiologic concentrations of 17β-estradiol. Here, we investigated the...

  • A natural compound from Hydnophytum formicarium induces apoptosis of MCF-7 cells via up-regulation of Bax. Abdullah, Hasmah; Pihie, Azimahtol Hawariah Lope; Hohmann, Judit; Molnár, Joseph // Cancer Cell International;2010, Vol. 10, p14 

    Background: Hydnophytum formicarium Jack is an epyphytic shrub that belongs to the family of Rubiaceae and is native to the tropical rain forests of the Asean region, which includes Malaysia. A flavanoid derivative, 7, 3', 5'- trihydroxyflavanone (3HFD), isolated from H. formicarium has been...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics