Cytotoxicity of the new antimetabolite-bisphosphonate (5-FdU-alendronate) in comparison to standard therapeutics on breast and ovarian cancer cell lines in the ATP tumor chemosensitivity assay

Excerpt

Bisphosphonates (BPs) are bone specific palliative therapeutics that reduce tumor- and cancer treatment-induced skeletal complication [1‐3]. Further, they are an effective treatment for preventing skeletal-related events in patients with bone metastasis and may preserve functional independence as well as quality of life. Besides their action on osteoclasts short-term treatment with zoledronic acid has a clear anti-tumour effect on breast cancer cells which is supposed to be mediated by inhibiting the mevalonate pathway [4, 5]. All BPs share a common P-C-P “backbone” with two phosphonate (PO₃) groups covalently linked to carbon. BPs are analogues of pyrophosphates where the P-O-P linkage is replaced by P-C-P. The central carbon atom is generally linked to two geminate phosphates, a tertiary hydroxyl group and a variable side chain. The chemical properties, the mode of action and the therapeutic efficacy are more or less determined by the variable side chain. The tertiary hydroxyl group supports the bone-binding of the geminate phosphate groups. …