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

  • Authors:
    • Keiko Suyama
    • Yoshihiko Noguchi
    • Tomoaki Tanaka
    • Tomohiko Yoshida
    • Takahisa Shibata
    • Yasushi Saito
    • Ichiro Tatsuno
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/or.18.5.1291
  • Pages: 1291-1298
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.

Related Articles

Journal Cover

November 2007
Volume 18 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Suyama K, Noguchi Y, Tanaka T, Yoshida T, Shibata T, Saito Y and Tatsuno I: 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. Oncol Rep 18: 1291-1298, 2007
APA
Suyama, K., Noguchi, Y., Tanaka, T., Yoshida, T., Shibata, T., Saito, Y., & Tatsuno, I. (2007). 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. Oncology Reports, 18, 1291-1298. https://doi.org/10.3892/or.18.5.1291
MLA
Suyama, K., Noguchi, Y., Tanaka, T., Yoshida, T., Shibata, T., Saito, Y., Tatsuno, I."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". Oncology Reports 18.5 (2007): 1291-1298.
Chicago
Suyama, K., Noguchi, Y., Tanaka, T., Yoshida, T., Shibata, T., Saito, Y., Tatsuno, I."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". Oncology Reports 18, no. 5 (2007): 1291-1298. https://doi.org/10.3892/or.18.5.1291