The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro
| Autor: | Christoph C. Geilen, Monika Raisova, Christian Riebeling, Forsea Am, C. E. Orfanos |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Osteolysis medicine.medical_treatment Pamidronate Antineoplastic Agents Biology Rho proteins Bone resorption Prenylation melanoma Tumor Cells Cultured medicine Humans Experimental Therapeutics bisphosphonates Diphosphonates Caspase 3 Cell growth Melanoma apoptosis Pamidronic acid Bisphosphonate Genes p53 medicine.disease Enzyme Activation Proto-Oncogene Proteins c-bcl-2 Oncology Apoptosis Caspases Mutation Immunology Cancer research Diterpenes Cell Division medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600476 |
| Popis: | Pamidronate belongs to the class of nitrogen-containing bisphosphonates that are potent inhibitors of bone resorption frequently used for the treatment of osteoporosis and cancer-induced osteolysis. The inhibition of osteoclasts’ growth has been suggested as the main mechanism of the inhibitory effect of pamidronate on bone metastases. Recent findings indicated that bisphosphonates also have a direct apoptotic effect on other types of tumour cells. Nitrogen-containing bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus blocking the synthesis of higher isoprenoids. By this mechanism they inactivate monomeric G-proteins of the Ras and Rho families for which prenylation is a functional requirement. On the background of the known key role of G-proteins in tumorigenesis, we investigated a possible beneficial use of pamidronate in the treatment of malignant melanoma. Our results indicate that pamidronate inhibits the cell growth and induces apoptosis in human melanoma cells in vitro. Susceptibility to pamidronate did not correlate to CD95 ligand sensitivity or p53 mutational status. Furthermore it is interesting to note that overexpression of bcl-2 did not abolish pamidronate-induced apoptosis. These data suggests that pamidronate has a direct anti-tumour effect on malignant melanoma cells, independently of the Bax/Bcl-2 level. British Journal of Cancer (2002) 87, 366–371. doi:10.1038/sj.bjc.6600476 www.bjcancer.com © 2002 Cancer Research UK |
| Databáze: | OpenAIRE |
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