Journal
CANCER LETTERS
Volume 287, Issue 1, Pages 109-116Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.06.003
Keywords
Breast cancer; OPG; TRAIL; Zoledronic acid
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Funding
- Deutsche Forschungsgemeinschaft [1875/5-2]
- Wilhelm Sander-Stiftung [2007.005.1]
- Novartis
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Breast cancer has a propensity to metastasize to bone, thus causing pathological fractures. Bisphosphonates are established drugs in the treatment of bone metastasis that inhibit osteoclast activity and interrupt the vicious cycle of osteoclast-tumor cell interactions. We evaluated the direct effects of zoledronic acid on estrogen receptor (ER)-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells. While zoledronic acid (100 PM) inhibited MDA-MB-231 cell proliferation after 72 h, and induced apoptosis via activation of caspase-3 and -7, it had only minor effects on MCF-7 cells. In addition, zoledronic acid induced apoptosis by up-regulating TNF-related apoptosis-inducing ligand (TRAIL) in MDA-MB-231 cells (p < 0.01), but had no effect on the expression of its decoy receptor osteoprotegerin (OPG). In MCF-7 cells, both cytokines were suppressed by zoledronic acid. In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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