Abstract 4261: Anti-angiogenic effects of zoledronic acid on osteotropic breast cancer cells

Emerging data suggest the bisphosphonate, zoledronic acid (ZOL), exerts both indirect and direct anti-tumoral effects by decreasing tumor cell proliferation, increasing apoptosis, and inhibiting angiogenesis. Recent data indicate that anti-angiogenic factors exert cellular effects via suppression of mitochondrial oxidative phosphorylation/respiration and elevation of intracellular ROS levels. This project intended to define proteins involved in response to ZOL-treatment of an osteotropic breast cancer cell line, MDA-231BO. Results demonstrate that MDA-231BO cells are more sensitive to ZOL cytotoxicity and salutary effects are both media- and calcium-dependent. To investigate pro-apoptotic mechanisms of ZOL, total RNA, whole cell protein lysates, or mitochondrial-enriched fractions were isolated from MDA-231BO cells and using a combination of RT-PCR, 1D/2D-PAGE separation and MALDI-MS/MS, we identified several angiogenesis inhibitors that were upregulated and pro-angiogenic factors that were downregulated after ZOL treatment. Functional studies demonstrate the improved efficacy of ZOL on MDA-231BO compared to MDA-MB-231 controls. Taken together, these results further support a model that ZOL tips the ‘angiogenic switch’ in favor of anti-angiogenic factors in cancer cells with a propensity for bone metastases. Partial research support came from NIH 5P20MD002732 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4261. doi:10.1158/1538-7445.AM2011-4261