Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation
| Autor: | Akira Kido, Hiromasa Fujii, Manabu Akahane, Yasuhito Tanaka, Kazuhiro Yoshitani, Kanya Honoki |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Cell Survival Cathepsin K Motility Connexin Bone Neoplasms Oleic Acids Bone resorption Pathology and Forensic Medicine Cell Movement Cell Line Tumor Internal medicine Biomarkers Tumor medicine Humans Neoplasm Invasiveness Bone Resorption Fibrosarcoma Osteosarcoma Osteoblasts Alendronate Bone Density Conservation Agents Chemistry Cell Biology medicine.disease Gene Expression Regulation Neoplastic Endocrinology Cell culture Connexin 43 Toxicity Cancer research HT1080 |
| Zdroj: | Pathology - Research and Practice. 207:417-422 |
| ISSN: | 0344-0338 |
| DOI: | 10.1016/j.prp.2011.04.007 |
| Popis: | Bisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were rather higher than those of untreated controls. Since this tendency was most evident, HOS was used for further assays, including cellular motility, bone resorption activity, and cathepsin K activity. The low-concentration of alendronate enhanced cellular viability and motility, which correlated with the expression of connexin 43 at the mRNA and protein levels. Interestingly, oleamide, a potent connexin 43 inhibitor, had an inhibitory effect on the enhanced proliferation. Our data suggest that alendronate may enhance the proliferation of osteoblastic cell line through connexin 43 activation. |
| Databáze: | OpenAIRE |
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