“…The stronger antiproliferative and/or proapoptotic effect of nitrogen-containing bisphosphonates compared to nonaminobisphosphonates was also reported in other cell types such as macrophages (Benford et al , 1999; Rogers et al , 1999), breast cancer cells (Senaratne et al , 2000), multiple myeloma (Shipman et al , 1998; Shipman et al , 2000) or colon adenocarcinoma (Suri et al , 2001), and this effect appears to be related to the ability of nitrogen-containing bisphosphonates to inhibit the mevalonate pathway and thereby the prenylation of signalling proteins such as the small GTPases. Both pamidronate and zoledronate were shown to inhibit specifically the enzyme FPP synthase (Bergstrom et al , 2000; Dunford et al , 2001), and the depletion of cellular pools of GGPP and FPP has been demonstrated to be a key mechanism in the induction of apoptosis and reduction of cell viability by nitrogen-containing bisphosphonates (Benford et al , 1999; Jagdev et al , 2001; Reszka et al , 2001).…”