Bisphosphonates are a class of drugs commonly used to prevent the loss of bone mass due to osteoporosis and other diseases related to the disorder of calcium homeostasis. Bisphosphonates have also been shown to possess anti-tumour activity when applied alone or in combination with known cytostatics. In clinics, bisphosphonates are usually applied in complementary treatment of cancer patients since they are very potent modifiers of a progression of skeletal metastasis in several forms of cancer, especially breast cancer. It is postulated that bisphosphonates decrease the rate of bone resorption not only due to their direct effect on osteoclasts, but also through the impact on macrophages present in microenvironment of tumour metastases. 

In these studies, we evaluate the anti-proliferative activity of a new bisphosphonate (naphthyl-1,5-diaminobis(methylidenebisphospho- nic) acid) on MCF-7 human breast cancer cells and J774E mouse macrophages. Naphthyl-1,5-diaminobis(methylidenebisphosphonic) acid exerted a potent, anti-proliferative effect on J774E cells with IC₅₀ values over 10 times lower as compared to zoledronic acid – a control bisphosphonate. For MCF-7 cells IC₅₀ values were respectively twice higher than for zoledronic acid. Moreover, it showed an additive or even synergistic anti-proliferative effect when applied in combination with cisplatin or doxorubicin. Interestingly, the effect was manifested the most distinctly when MCF-7 or J774E cells were treated with naphthyl-1,5-diaminobis(methylidenebisphosphonic) acid and cytostatics simultaneously or were pre-treated with cytostatics.

We also evaluated the influence of naphthyl-1,5-diamino- bis(methylidenebisphosphonic) acid on the adhesive and migratory properties of MCF-7 or J774E cells. An inhibitory effect of naphthyl-1,5-diaminobis(methylidenebisphosphonic) acid on cell adhesion to fibrinogen and migration through matrigel was observed.

In summary, naphthyl-1,5-diaminobis(methylidenebisphosphonic) acid seems to be of particular interest for further studies concerning the influence of bisphosphonates on cells involved in tumour development and progression.

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