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


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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.



Key Engineering Materials (Volumes 529-530)

Main Theme:

Edited by:

Kunio Ishikawa and Yukihide Iwamoto




T. Inayama et al., "Studies on the Anti-Tumor Action of Chelate-Setting Apatite Cements", Key Engineering Materials, Vols. 529-530, pp. 178-182, 2013

Online since:

November 2012




[1] K. Kato, H. Aoki, T. Tabata, M. Ogiso, Biocompatibility of apatite ceramics in mandibles, Biomater. Med. Devices Artif. Organs. 7 (1979) 291-297.


[2] A. Uchida, N. Araki, Y. Shinto, H. Yoshikawa, E. Kurisaki, K. Ono, The use of calcium hydroxyapatite ceramic in bone-tumor surgery, J. Bone Joint Surg. Br. 72 (1990) 298-302.


[3] Y. Miyamoto, K. Ishikawa, M. Takechi, T. Toh, T. Yuasa, M. Nagayama, K. Suzuki, Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing, J. Biomed. Mater. Res. 48 (1999).


[4] M. Aizawa, H. Shinoda, H. Uchida, K. Itatani, I. Okada, M. Matsumoto, Y. Toyama, Development and biological evaluation of apatite fibre scaffolds with large pore size and high porosity for bone regeneration, Bioceramics 15 240-2 (2003) 647-650.


[5] B.F. Harland G. Narula, Food phytate and its hydrolysis products, Nutr. Res. 19 (1999) 947-961.


[6] P.S. Rao, X.K. Liu, D.K. Das, G.S. Weinstein, D.H. Tyras, Protection of ischemic heart from reperfusion injury by myoinositol hexaphosphate, A Natural antioxidant, Ann. Thorac. Surg. 52 (1991) 908-912.


[7] N. Sasakawa, M. Sharif, M.R. Hanley, Metabolism and biological-activities of inositol pentakisphosphate and inositol hexakisphosphate, Biochem. Pharmacol. 50 (1995) 137-146.


[8] I. Vucenik, K. Tantivejkul, Z.S. Zhang, K.E. Cole, I. Saied, A.M. Shamsuddin, IP6 in treatment of liver cancer I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line, Anticancer Res. 18 (1998) 4083-4090.

[9] I. Vucenik, Z.S. Zhang, A.M. Shamsuddin, IP6 in treatment of liver cancer II. Intra-tumoral injection of IP6 regresses pre-existing human liver cancer xenotransplanted in nude mice, Anticancer Res. 18 (1998) 4091-4096.

[10] A.M. Shamsuddin G.Y. Yang, Inositol hexaphosphate inhibits growth and induces differentiation of Pc-3 human prostate-cancer cells, Carcinogenesis 16 (1995) 1975-(1979).


[11] K. Sakamoto, G. Venkatraman, A.M. Shamsuddin, Growth-inhibition and differentiation of Ht-29 cells in-vitro by inositol hexaphosphate (phytic acid), Carcinogenesis 14 (1993) 1815-1819.


[12] C.S. Huang, W.Y. Ma, S.S. Hecht, Z.G. Dong, Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3' kinase, Cancer Res. 57 (1997) 2873-2878.

[13] L.U. Thompson L. Zhang, Phytic acid and minerals - Effect on early markers of risk for mammary and colon carcinogenesis, Carcinogenesis 12 (1991) 2041-(2045).


[14] Y. Banno, T. Sakai, T. Kumada, Y. Nozawa, Potentiation by cholera-toxin of bradykinin-induced inositol phosphate production in the osteoblast-like cell-line MC3T3-E1, Biochem. J. 292 (1993) 401-408.


[15] I. Vucenik, A. Passaniti, M.I. Vitolo, K. Tantivejkul, P. Eggleton, A.M. Shamsuddin, Anti-angiogenic activity of inositol hexaphosphate (IP6), Carcinogenesis 25 (2004) 2115-2123.


[16] Y. Horiguchi, A. Yoshikawa, K. Oribe, M. Aizawa, Fabrication of chelate-setting hydroxyapatite cements from four kinds of commercially-available powder with various shape and crystallinity and their mechanical property, J. Ceram. Sci. Jpn. 116 (2008).


[17] H. Konishi, Honda M, Aizawa M, Kanzawa N, Biochemical studies of the potential anti-tumor activity of novel chelate-setting apatite cements., Key Eng. Mater. 493-494 (2012) 678-683.