ArticleThe Journal of pharmacology and experimental therapeutics2010
A novel geranylgeranyl transferase inhibitor in combination with lovastatin inhibits proliferation and induces autophagy in STS-26T MPNST cells.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Neurofibromatosis Type 1 and the Search for Effective Tumor Therapies Using High-Throughput Drug Screening.Current oncology (Toronto, Ont.) · 2025Review
- Intratumoral injection of schwannoma with attenuatedProceedings of the National Academy of Sciences of the United States of America · 2022Article
- In vivo evaluation of combination therapy targeting the isoprenoid biosynthetic pathway.Pharmacological research · 2021Article
- Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B.International journal of molecular sciences · 2021Article
- CD55 upregulation in astrocytes by statins as potential therapy for AQP4-IgG seropositive neuromyelitis optica.Journal of neuroinflammation · 2019Article
- Ras and Rap1: A tale of two GTPases.Seminars in cancer biology · 2019Review
- Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer CellsBalkan medical journal · 2018Article
- Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury.Neural regeneration research · 2016Article
- Transcriptional profiling of breast cancer cells in response to mevinolin: Evidence of cell cycle arrest, DNA degradation and apoptosis.International journal of oncology · 2016Article
- Protein prenylation: unique fats make their mark on biology.Nature reviews. Molecular cell biology · 2016Review
- Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment.Journal of Cancer · 2016Review
- How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization.Mini reviews in medicinal chemistry · 2016Review
- Pharmacological Inhibition of Protein Lipidation.The Journal of membrane biology · 2015Review
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
- In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells.British journal of cancer · 2014Article
- Defects in mitochondrial clearance predispose human monocytes to interleukin-1β hypersecretion.The Journal of biological chemistry · 2014Article
- Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion.Journal of neuro-oncology · 2013Article
- Nifedipine prevents etoposide-induced caspase-3 activation, prenyl transferase degradation and loss in cell viability in pancreatic β-cells.Apoptosis : an international journal on programmed cell death · 2013Article
- Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.ISRN oncology · 2013Review
- Geranylgeranyltransferase I promotes human glioma cell growth through Rac1 membrane association and activation.Journal of molecular neuroscience : MN · 2013Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Prenylation inhibitors have gained increasing attention as potential therapeutics for cancer. Initial work focused on inhibitors of farnesylation, but more recently geranylgeranyl transferase inhibitors (GGTIs) have begun to be evaluated for their potential antitumor activity in vitro and in vivo. In this study, we have developed a nonpeptidomimetic GGTI, termed GGTI-2Z [(5-nitrofuran-2-yl)methyl-(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl 4-chlorobutyl(methyl)phosphoramidate], which in combination with lovastatin inhibits geranylgeranyl transferase I (GGTase I) and GGTase II/RabGGTase, without affecting farnesylation. The combination treatment results in a G(0)/G(1) arrest and synergistic inhibition of proliferation of cultured STS-26T malignant peripheral nerve sheath tumor cells. We also show that the antiproliferative activity of drugs in combination occurs in the context of autophagy. The combination treatment also induces autophagy in the MCF10.DCIS model of human breast ductal carcinoma in situ and in 1c1c7 murine hepatoma cells, where it also reduces proliferation. At the same time, there is no detectable toxicity in normal immortalized Schwann cells. These studies establish GGTI-2Z as a novel geranylgeranyl pyrophosphate derivative that may work through a new mechanism involving the induction of autophagy and, in combination with lovastatin, may serve as a valuable paradigm for developing more effective strategies in this class of antitumor therapeutics.
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Registered trials
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.