Studies on the Anti-Tumor Action of Chelate-Setting Apatite Cements

Abstract

Chelate-setting apatite cement is a novel biomaterial developed as a bone substitute. We previously reported a chelate-setting apatite cement, IP6-HAp, which exhibits anti-tumor activity via apoptotic cell death. However, our preliminary data showed that excess IP6 arrests osteoblast growth. We found that a high, transient amount of IP6 was released from the cement. We therefore hypothesized that a high performance cement specific for tumor cells can be developed by controlling the release of IP6 from the cement. To validate this, we used a murine calvarial osteoblast cell line (MC3T3-E1) and a human osteosarcoma cell line (HOS). Culturing HOS or MC3T3-E1 in medium containing various concentrations of IP6 more effectively arrested the growth of HOS than that of MC3T3-E1. Although the proliferation of osteoblasts was suppressed at early growth stages in response to the release of IP6 from the cements, there was no difference in the number of cells after a prolonged culture period. In contrast, osteosarcoma cell growth remained suppressed even after a prolonged culture period. To better understand why these two cell types respond differently to IP6, we investigated cell viability by measuring the ratio of living and dead cells. Our findings suggest that this novel bone graft cement will find unique uses due the different sensitivity of tumor cells and osteoblasts towards IP6.