ArticleBiochemical pharmacology2013
Ibandronate increases the expression of the pro-apoptotic gene FAS by epigenetic mechanisms in tumor cells.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines.International journal of molecular sciences · 2017Article
- Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate.The Journal of biological chemistry · 2016Article
- Antiresorptive therapy and risk of mortality and refracture in osteoporosis-related hip fracture: a nationwide study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells.Molecular carcinogenesis · 2016Article
- Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells.Cancer genetics · 2015Article
- Osteosarcoma Genetics and Epigenetics: Emerging Biology and Candidate Therapies.Critical reviews in oncogenesis · 2015Review
- Epigenetic alterations in osteosarcoma: promising targets.Molecular biology reports · 2014Review
- The effect of alendronate on proteome of hepatocellular carcinoma cell lines.International journal of proteomics · 2014Article
- A new bisphosphonate derivative, CP, induces gastric cancer cell apoptosis via activation of the ERK1/2 signaling pathway.Acta pharmacologica Sinica · 2013Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
There is growing evidence that aminobisphosphonates like ibandronate show anticancer activity by an unknown mechanism. Biochemically, they prevent posttranslational isoprenylation of small GTPases, thus inhibiting their activity. In tumor cells, activated RAS-GTPase, the founding member of the gene family, down-regulates the expression of the pro-apoptotic gene FAS via epigenetic DNA-methylation by DNMT1. We compared ibandronate treatment in neoplastic human U-2 osteosarcoma and in mouse CCL-51 breast cancer cells as well as in the immortalized non-neoplastic MC3T3-E1 osteoblastic cells. Ibandronate attenuated cell proliferation in all cell lines tested. In the neoplastic cells we found up-regulation of caspases suggesting apoptosis. Further we found stimulation of FAS-expression as a result of epigenetic DNA demethylation that was due to down-regulation of DNMT1, which was rescued by re-isoprenylation by both geranylgeranyl-pyrophosphate and farnesylpyrophosphate. In contrast, ibandronate did not affect FAS and DNMT1 expression in MC3T3-E1 non-neoplastic cells. Data suggest that bisphosphonates via modulation of the activity of small-GTPases induce apoptosis in neoplastic cells by DNA-CpG-demethylation and stimulation of FAS-expression. In conclusion the shown epigenetic mechanism underlying the anti-neoplastic activity of farnesyl-transferase-inhibition, also explains the clinical success of other drugs, which target this pathway.
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