Effects of clodronate on cancer growth and Ca²⁺ signaling of human thyroid carcinoma cell lines

Clodronate, one of the halogenated bisphosphonates, was found to inhibit the cell growth of endocytic macrophages, osteoclasts and several cancer cells through diverse mechanisms. Cytosolic Ca²⁺ signaling had previously been suggested as an apoptotic signal to certain cancer cells. Whether clodronate has an anti-cancer effect and induces the Ca²⁺ signal in thyroid cancer cells remains unknown. In this study, the effects of clodronate, including growth inhibition and cytosolic Ca²⁺ signaling, were examined and analyzed on ARO, SW579, WRO and TT thyroid cancer cell lines. Clodronate decreased the growth of these cells in a dose-dependent manner and was more effective on slow growing cells. Clodronate treatment transiently increased cytosolic Ca²⁺ on slow growing SW579 thyroid cancer cells but not on the fast growing ARO cells. The results from this study implied that clodronate-mediated cell growth inhibition in slow growing thyroid cancer cells might correlate with a Ca²⁺ signaling pathway.