The alkynylphosphonate analogue of calcitriol EM1 has potent anti-metastatic effects in breast cancer

• EM1 reduces the number of lung metastases in an animal model of breast cancer.
• EM1 inhibits cellular migration and invasion in a breast carcinoma cell line.
• EM1 upregulates E-cadherin expression in a breast carcinoma cell line.
• EM1 does not affect the migration of a non-malignant mammary cell line.
• EM1 maintains plasma calcium within the normal levels at a 50 μg/kg body weight dose.

The active form of vitamin D3, calcitriol, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and prodifferentiating agent. However, when effective antitumor doses of calcitriol are employed, hypercalcemic effects are observed, thus precluding its therapeutic application. To overcome this problem, structural analogues have been designed with the aim at retaining or even increasing the antitumor effects while decreasing its calcemic activity. This report shows the biological evaluation of an alkynylphosphonate vitamin D less-calcemic analogue in a murine model of breast cancer. We demonstrate that this compound has potent anti-metastatic effects through its action over cellular migration and invasion likely mediated through the up-regulation of E-cadherin expression. Based on the current in vitro and in vivo results, EM1 is a promising candidate as a therapeutic agent in breast cancer.

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