The present study was aimed to investigate the effect of tumstatin on inhibition of proliferation and induction of apoptosis in Saos-2 human osteosarcoma cells and to understand the mechanism involved. Inhibition of cell proliferation was analyzed by MTT assay and induction of apoptosis through nuclear fragmentation assay. Viability of Saos-2 cells was reduced to 19% on treatment with 25 mu M concentration of tumstatin after 48 h. Presence of characteristic apoptotic nuclei, rounded cell shape and shrunken size were caused by tumstatin treatment at 25 mu M concentration. The level of mRNA corresponding to PTEN, FasR and FasL was increased significantly in tumstatin treated Saos-2 cells compared to untreated control. Investigation of the mechanism revealed NF-kappa B activation by phosphorylation on serine 536. The activated NF-kappa B was translocated into the nucleus from the cytoplasm on treatment with tumstatin. Degradation of the I kappa B alpha by tumstatin was found to be much slower compared to that induced by treatment with TNF-alpha. Thus, tumstatin inhibits proliferation and induces apoptosis in Saos-2 cells through activation of NF-kappa B and its translocation to the nucleus. Therefore, tumstatin can play an important role in the treatment of osteosarcoma.
[1]Jilin Univ, China Japan Union Hosp, Dept Orthopaed, Changchun 130033, Jilin, Peoples R China.
[2]Daqing Oilfields Gen Hosp, Dept Orthoped, Daqing 163000, Heilongjiang, Peoples R China.
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