Int J Mol Med 2014 Oct 4;34(4):1051-6. Epub 2014 Aug 4.
Chronic Disease Research Center, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
The inhibition of topoisomerase can suppress the growth of cancer cells and induce apoptosis. The aim of this study was to evaluate the anticancer effects and mechanisms of action of a novel topoisomerase inhibitor, 4-(furan-2-yl)-2-(pyridin-2-yl)-5,6-dihydro-1,10-phenanthroline (FPDHP). FPDHP suppressed the growth of Caki, A549, HT29 and MDA-MB-231 cells, and induced caspase-dependent apoptosis in the Caki cells. In particular, FPDHP also induced caspase-dependent apoptosis and the downregulation of the protein expression levels of cellular FLICE-like inhibitory protein (cFLIP) and the phosphorylation of Akt in Caki cells. Notably, the overexpression of cFLIP, but not that of Akt, in part, blocked the FPDHP-mediated apoptosis in Caki cells. In addition, FPDHP was further shown to induce the caspase-independent detachment of Caki cells from the culture dish; higher populations of apoptotic cells were observed in the detached cells than in the attached cells. To the best of our knoweledge, these results collectively demonstrate for the first time that FPDHP has a killing effect on Caki cells, which is mediated through both caspase-dependent apoptosis and caspase-independent cell detachment.