ArticleOncogene2004
The farnesyl transferase inhibitor R115777 (Zarnestra) synergistically enhances growth inhibition and apoptosis induced on epidermoid cancer cells by Zoledronic acid (Zometa) and Pamidronate.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 74 citations in OpenAlex.
- Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk.British journal of cancer · 2010Trial
- Personalized Drug Screening and Risk Assessment in Patient-Derived Gastroenteropancreatic Neuroendocrine Neoplasms.The Journal of clinical endocrinology and metabolism · 2026Article
- Synthesis of Tetrasubstituted Phosphorus Analogs of Aspartic Acid as Antiproliferative Agents.Molecules (Basel, Switzerland) · 2022Article
- Zoledronic acid-loaded lipidic nanoparticles enhance apoptosis and attenuate invasiveness by inhibiting epithelial to mesenchymal transition (EMT) in HepGNaunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Bisphosphonate-Based Conjugates and Derivatives as Potential Therapeutic Agents in Osteoporosis, Bone Cancer and Metastatic Bone Cancer.International journal of molecular sciences · 2021Review
- Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review.BMC cancer · 2020Review
- Bisphosphonate conjugation for bone specific drug targeting.Bone reports · 2018Review
- Pamidronate decreases bilirubin-impaired cell death and improves dentinogenic dysfunction of stem cells from human deciduous teeth.Stem cell research & therapy · 2018Article
- Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Zoledronate can promote apoptosis and inhibit the proliferation of colorectal cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies.Oncotarget · 2015Review
- Article
- Proteomic analysis of zoledronic-acid resistant prostate cancer cells unveils novel pathways characterizing an invasive phenotype.Oncotarget · 2015Article
- Nanoparticles for the delivery of zoledronic acid to prostate cancer cells: a comparative analysis through time lapse video-microscopy technique.Cancer biology & therapy · 2014Article
- Myeloid-derived suppressor cells in multiple myeloma: pre-clinical research and translational opportunities.Frontiers in oncology · 2014Review
- Acquired resistance to zoledronic acid and the parallel acquisition of an aggressive phenotype are mediated by p38-MAP kinase activation in prostate cancer cells.Cell death & disease · 2013Article
- Bisphosphonates and cancer: what opportunities from nanotechnology?Journal of drug delivery · 2013Article
- Stathmin is involved in the cooperative effect of Zoledronic acid and gefitinib on bone homing breast cancer cells in vitro.Journal of bone oncology · 2012Article
- Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells.Journal of cellular and molecular medicine · 2012Article
- CCN1, a candidate target for zoledronic acid treatment in breast cancer.Molecular cancer therapeutics · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pamidronate (PAM) and zoledronic acid (ZOL) are aminobisphosphonates (BPs) able to affect the isoprenylation of intracellular small G proteins. We have investigated the antitumor activity of BPs and R115777 farnesyl transferase inhibitor (FTI) against epidermoid cancer cells. In human epidermoid head and neck KB and lung H1355 cancer cells, 48 h exposure to PAM and ZOL induced growth inhibition (IC(50) 25 and 10 microM, respectively) and apoptosis and abolished the proliferative and antiapoptotic stimuli induced by epidermal growth factor (EGF). In these experimental conditions, ZOL induced apoptosis through the activation of caspase 3 and a clear fragmentation of PARP was also demonstrated. A strong decrease of basal ras activity and an antagonism on its stimulation by EGF was recorded in the tumor cells exposed to BPs. These effects were paralleled by impaired activation of the survival enzymes extracellular signal regulated kinase 1 and 2 (Erk-1/2) and Akt that were not restored by EGF. Conversely, farnesol induced a recovery of ras activity and antagonized the proapoptotic effects induced by BPs. The combined treatment with BPs and R115777 resulted in a strong synergism both in growth inhibition and apoptosis in KB and H1355 cells. The synergistic activity between the drugs allowed BPs to produce tumor cell growth inhibition and apoptosis at in vivo achievable concentrations (0.1 micromolar for both drugs). Moreover, the combination was highly effective in the inhibition of ras, Erk and Akt activity, while farnesol again antagonized these effects. In conclusion, the combination of BPs and FTI leads to enhanced antitumor activity at clinically achievable drug concentrations that resides in the inhibition of farnesylation-dependent survival pathways and warrants further studies for clinical translation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.