Abstract 2655: Visualization of G1 arrest of cell cycle induced by inhibition of PI-3 kinase in cancer cells: in vitro evaluations

Abstract

Abstract The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in cancer, and is considered as a promising therapeutic target of cancer therapy. Since PI3K pathway mediates growth- and anti-apoptotic signals, inhibition of PI3K is expected to induce apoptosis and/or growth arrest in cancer cells. We previously developed Fluorescent Ubiquitination-based Cell Cycle Indicator (Fucci) system to enable real-time visualization of cell cycle progression in live cells. Taking advantage of Fucci system, we examined cell cycle progression after treatment of various PI3K inhibitors by using a time-lapse fluorescent microscope. As a result, we could visualize the induction of G1 arrest of cell cycle in breast cancer MCF-7 cells within 24 h after treatment with ZSTK474, and the G1 arrest lasted at least 48 h. Similar results were obtained after treatment with other PI3K inhibitors such as NVP-BEZ235 and GDC-0941. These results clearly indicate that PI3K inhibitors exert antitumor activity via a cytostatic mechanism by inducing G1 arrest of cell cycle. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2655. doi:10.1158/1538-7445.AM2011-2655