TY - JOUR AB - Bisphosphonates cause apoptosis to various types of cancer cells including breast cancer. Inhibition of the mevalonate pathway was reported to be involved in the apoptosis induced by bisphosphonates, but its precise mechanism has not been unveiled. In the present study, we investigated the molecular mechanism of risedronate, a bisphosphonate, in the apoptosis of the breast cancer cell line MCF-7 in comparison with that of cerivastatin, an HMG CoA reductase inhibitor (statin), since statin has been known to induce apoptosis through an isoprenoid-dependent pathway in these cells. We found that i) risedronate induced MCF-7 cells into apoptosis in a manner similar to cerivastatin with the activation of caspase-9 followed by caspase-6 and -7, that ii) bisphosphonate-induced apoptosis was significantly, but not fully, recovered by the addition of GGOH, an isoprenoid, which completely rescued in case of cerivastatin-induced apoptosis, that iii) risedronate induced G2 arrest with the induction of Bim (BH3-only protein), but that statin induced G1 arrest without it, and that iv) the down-regulation of Bim protein by siRNA significantly attenuated the risedronate-induced apoptosis. These data clearly indicate that both isoprenoid-dependent and -independent pathways might be involved in the apoptosis induced by bisphosphonate, and Bim might be a critical component for the isoprenoid-independent apoptotic pathway. AD - Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan null AU - Suyama,Keiko AU - Noguchi,Yoshihiko AU - Tanaka,Tomoaki AU - Yoshida,Tomohiko AU - Shibata,Takahisa AU - Saito,Yasushi AU - Tatsuno,Ichiro DA - 2007/11/01 DO - 10.3892/or.18.5.1291 EP - 1298 IS - 5 JO - Oncol Rep PY - 2007 SN - 1021-335X 1791-2431 SP - 1291 ST - Isoprenoid-independent pathway is involved in apoptosis induced by risedronate, a bisphosphonate, in which Bim plays a critical role in breast cancer cell line MCF-7 T2 - Oncology Reports TI - Isoprenoid-independent pathway is involved in apoptosis induced by risedronate, a bisphosphonate, in which Bim plays a critical role in breast cancer cell line MCF-7 UR - https://doi.org/10.3892/or.18.5.1291 VL - 18 ER -