Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

Molecular Cancer

Research

Masood A Shammas¹  Donald W Weaver¹  Madhu Prasad¹  Ravindra B Potti¹  Jagannath Pal¹  Jay Shah¹  Sreedhar Chamala²  Ramesh B Batchu²  Christopher Steffes²  Aamer M Qazi²  Assaad Semaan³  Shelly Seward³  Mahdi Haider³  Sanjeev Kumar⁴  Robert Morris⁴  Christopher S Bryant⁴ 

[1] Department of Surgery, Wayne State University, 4100 John R Street, 48201, Detroit, MI, USA;Department of Surgery, Wayne State University, 4100 John R Street, 48201, Detroit, MI, USA;Karmanos Cancer Institute, Wayne State University, 4100 John R Street, 48201, Detroit, MI, USA;Dept of Ob/Gyn, Wayne State University, 4100 John R Street, 48201, Detroit, MI, USA;Dept of Ob/Gyn, Wayne State University, 4100 John R Street, 48201, Detroit, MI, USA;Karmanos Cancer Institute, Wayne State University, 4100 John R Street, 48201, Detroit, MI, USA;

关键词: Paclitaxel;    Cell Cycle Progression;    Annexin Versus;    Ovarian Cancer Cell;    Ovarian Cancer Cell Line;   

DOI  :  10.1186/1476-4598-9-47

 received in 2009-09-01, accepted in 2010-03-02,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.ResultsSFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex.ConclusionsSFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

【 授权许可】

Unknown   
© Bryant et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.