Biochemical Studies of the Potential Anti-Tumor Activity of Novel Chelate-Setting Apatite Cements

Abstract:

The anti-tumor activity of hydroxyapatite (HAp) cements, which had been developed using a novel setting mechanism termed chelate bonding, against the human osteosarcoma cell line (HOS) and rat bone marrow stromal cells (BMSC) was examined. We aimed to understand the mechanism of the anti-tumor activity of the cement, thereby facilitating improvement of its biological activity. HAp powders were surface-modified with three different concentrations of inositol hexaphosphate (IP6), which were then used to fabricate three different IP6-HAp cements. The amount of IP6 that was bound to the HAp powder, and the amount that was released from the HAp cement, was measured for each sample. Approximately 1/200 to 1/1600 of the bound IP6 was released into the culture medium by day 4. Surface-modification of HAp with high concentration of IP6 inhibits the proliferation of both HOS cells and BMSCs, and appears to induce their apoptotic cell death. HOS cells were slightly more sensitive to IP6 than BMSCs. Thus, novel, chelate-bonded HAp cements are a candidate bone substitution material that exhibit anti-tumor activity.

• Periodical: Key Engineering Materials (Volumes 493-494)
• Pages: 315-319
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.493-494.315
• Online since: October 2011
• Authors: Hidenori Konishi, Michiyo Honda, Mamoru Aizawa, Nobuyuki Kanzawa
• Keywords: Anti-Tumor Activity, Apoptosis, Chelate-Bond, Hydroxyapatite Cement, Inositol Hexaphosphate

References

[1] A. Matsumine, A. Myoui, K. Kusuzaki, N. Araki, M. Seto, H. Yoshikawa, A. Uchida, Calcium hydroxyapatite ceramic implants in bone tumour surgery - A long-term follow-up study, J. Bone Joint Surg. Br. 86B (2004) 719-725.

DOI: 10.1302/0301-620x.86b5.14242

[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.

DOI: 10.1302/0301-620x.72b2.2155908

[3] M. Aizawa, Y. Haruta, I. Okada, Development of novel cement processing using hydroxyapatite particles modified with inositol phosphate, Arch. BioCeram. Res. 3 (2003) 134-138.

[4] 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. Soc. Japan 116 (2008).

DOI: 10.2109/jcersj2.116.50

[5] 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).

DOI: 10.1002/(sici)1097-4636(1999)48:1<36::aid-jbm8>3.0.co;2-i

[6] V. Raboy, myo-Inositol-1, 2, 3, 4, 5, 6-hexakisphosphate, Phytochemistry 64 (2003) 1033-1043.

DOI: 10.1016/s0031-9422(03)00446-1

[7] F. Lemtiri-Chlieh, E.A.C. MacRobbie, C.A. Brearley, Inositol hexakisphosphate is a physiological signal regulating the K+-inward rectifying conductance in guard cells, Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 8687-8692.

DOI: 10.1073/pnas.140217497

[8] F.S. Menniti, K.G. Oliver, J.W. Putney, Jr., S.B. Shears, Inositol phosphates and cell signaling: new views of InsP5 and InsP6, Trends Biochem. Sci. 18 (1993) 53-56.

DOI: 10.1016/0968-0004(93)90053-p

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

DOI: 10.1016/0006-2952(95)00059-9

[10] A.M. Shamsuddin, A.M. Elsayed, A. Ullah, Suppression of large intestinal cancer in F344 rats by inositol hexaphosphate, Carcinogenesis 9 (1988) 577-580.

DOI: 10.1093/carcin/9.4.577

[11] C.H. Fox, M. Eberl, Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review, Complement. Ther. Med. 10 (2002) 229-234.

DOI: 10.1016/s0965-2299(02)00092-4

[12] A.M. Shamsuddin, I. Vucenik, K.E. Cole, IP6: A novel anti-cancer agent, Life Sci. 61 (1997) 343-354.

DOI: 10.1016/s0024-3205(97)00092-1

[13] S. Takahashi, T. Konishi, K. Nishiyama, M. Mizumoto, M. Honda, Y. Horiguchi, K. Oribe, M. Aizawa, Fabrication of novel bioresorbable beta-tricalcium phosphate cement on the basis of chelate-setting mechanism of inositol phosphate and its evaluation, J. Ceram. Soc. Japan 119 (2011).

DOI: 10.2109/jcersj2.119.35

[14] G.L. Deliliers, F. Servida, N.S. Fracchiolla, C. Ricci, C. Borsotti, G. Colombo, D. Soligo, Effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells, Brit. J. Haematol. 117 (2002) 577-587.

DOI: 10.1046/j.1365-2141.2002.03453.x