The Farnesyltransferase Inhibitor, FTI-2153, Blocks Bipolar Spindle Formation and Chromosome Alignment and Causes Prometaphase Accumulation during Mitosis of Human Lung Cancer Cells

Abstract

Even though farnesyltransferase inhibitors (FTIs), a novel class of therapeutic agents presently in clinical trials, have preclinically outstanding anticancer activity and impressive lack of toxicity, their mechanism of action is not well understood. To enhance our understanding of how FTIs inhibit the growth of tumors, we have investigated their effects on cell cycle progression of two human lung cancer cell lines, A-549 and Calu-1. In this report, we show in synchronized A-549 and Calu-1 cells that FTI-2153 treatment resulted in a large accumulation of cells in the mitosis phase of the cell division cells in the and that the accumulation in mitosis is the of cells FTI-2153 the of A-549 and Calu-1 cells and of FTI-2153 a and this that cells their the FTI-2153 not the the of two and a mechanism FTIs inhibit progression mitosis and growth is and Even though farnesyltransferase inhibitors (FTIs), a novel class of therapeutic agents presently in clinical trials, have preclinically outstanding anticancer activity and impressive lack of toxicity, their mechanism of action is not well understood. To enhance our understanding of how FTIs inhibit the growth of tumors, we have investigated their effects on cell cycle progression of two human lung cancer cell lines, A-549 and Calu-1. In this report, we show in synchronized A-549 and Calu-1 cells that FTI-2153 treatment resulted in a large accumulation of cells in the mitosis phase of the cell division cells in the and that the accumulation in mitosis is the of cells FTI-2153 the of A-549 and Calu-1 cells and of FTI-2153 a and this that cells their the FTI-2153 not the the of two and a mechanism FTIs inhibit progression mitosis and growth is and farnesyltransferase farnesyltransferase the of the the of that a their and and not in is the and of in is a of and cell the the cell division cell and in of human in and cell in farnesyltransferase that farnesyltransferase inhibitors anticancer in the have resulted in and FTIs in of and well of and of the FTIs inhibit farnesyltransferase in in the and in cells and in of FTIs of human cancer cells in the of a mechanism in the FTIs have inhibitors of growth in impressive activity and lack of cells have human clinical FTIs in the mechanism FTIs their outstanding activity FTIs inhibit growth that the not of human FTIs in the of in human tumors, in the of FTIs FTIs and inhibitors of FTIs of the growth in of human the of of not that of of that is and a activity in in human cancer cells of a and and human growth in the FTIs not the mechanism of action of FTIs we have the effects of FTIs on cell cycle progression of human cancer is the of the cell cycle a we a this we that in is not phase In in human cancer cells we that FTIs a cells in have on cell cycle on the cell we show and synchronized human lung cancer that FTIs a and that the of and and a accumulation of the cells in synchronized human lung cancer cells in and To the effects of of on cell cycle we have a cells cells in treatment the and the the of the human cancer cells in the of the farnesyltransferase FTI-2153 in the of A-549 cells and phase and and and a cycle and and In A-549 cells in the of FTI-2153 in their the and the and cells in and cells and in and cells and and of cells and FTI-2153 treatment 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