The cell cycle arrest and the anti-invasive effects of nitrogen-containing bisphosphonates are not mediated by DBF4 in breast cancer cells

4^th World Congress on Cancer Science & Therapy

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Fatemeh Elahian

Accepted Abstracts: J Cancer Sci Ther

Abstract :

Introduction: DBF4 is an essential protein kinase required for DNA replication and plays a critical role in the S-phase checkpoint. It is also required for cell surface adhesion. Yeast DBF4 analog (YDR052C) may be a target of nitrogen-containing bisphosphonates (NBPs) and anti-invasive and S-phase arrest-inducing effects of NBPs may be mediated via this protein. Objectives: Further studies are needed to confirm these mechanisms in human cells. Aims: The present study focuses on analysis of the relationship between NBPs treatment and DBF4 expression levels in human breast cancer cells and the consequences on the cell cycle and migration behavior. Methods: The effects of Pamidronate, risedronate, or zoledronate on BT20, MDA-MB231 and T47D cell viability and DBF4 expression were measured via MTT assays and western blotting. FACS cell cycle analyses and invasion assays were conducted in cells in the presence of NBPs to identify any correlations between DBF4 expression and S-phase arrest or anti-invasive effects of the bisphosphonates. Results: Zoledronate transiently down-regulated DBF4 expression in all cell lines, but after 72 h, DBF4 expression returned to the control levels. Following treatment of the tumor cells, the number of cells in S-phase was increased. Pamidronate and zoledronate showed anti-invasive effects in BT20 cells. The MDA-MB231 cells appear to be more invasive, as a reduction of invasiveness was only observed after 72 h of the drug exposure. Conclusions: We finally concluded that the anti-invasive and cell cycle arrest-inducing effects NBPs are not DBF4 mediated, and other mediators are therefore needed to explain the observed complex behaviors.