ArticleThe Journal of pharmacology and experimental therapeutics2008
Induction of apoptosis in neurofibromatosis type 1 malignant peripheral nerve sheath tumor cell lines by a combination of novel farnesyl transferase inhibitors and lovastatin.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- Neurofibromatosis Type 1 and the Search for Effective Tumor Therapies Using High-Throughput Drug Screening.Current oncology (Toronto, Ont.) · 2025Review
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- Review
- In vivo evaluation of combination therapy targeting the isoprenoid biosynthetic pathway.Pharmacological research · 2021Article
- Review
- Ras and Rap1: A tale of two GTPases.Seminars in cancer biology · 2019Review
- How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization.Mini reviews in medicinal chemistry · 2016Review
- Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.ISRN oncology · 2013Review
- A retroperitoneal NF1-independent malignant peripheral nerve sheath tumor with elevated serum CA125: case report and discussion.Journal of neuro-oncology · 2012Article
- Aborted autophagy and nonapoptotic death induced by farnesyl transferase inhibitor and lovastatin.The Journal of pharmacology and experimental therapeutics · 2011Article
- Simvastatin overcomes the resistance to serum withdrawal-induced apoptosis of lymphocytes from Alzheimer's disease patients.Cellular and molecular life sciences : CMLS · 2010Article
- The role of neurofibromin in N-Ras mediated AP-1 regulation in malignant peripheral nerve sheath tumors.Molecular and cellular biochemistry · 2010Article
- A novel geranylgeranyl transferase inhibitor in combination with lovastatin inhibits proliferation and induces autophagy in STS-26T MPNST cells.The Journal of pharmacology and experimental therapeutics · 2010Article
- [Cutaneous malignant peripheral nerve sheath tumor in neurofibromatosis type 1].Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2009Article
- Working together: Farnesyl transferase inhibitors and statins block protein prenylation.Molecular and cellular pharmacology · 2009Article
- Suppression of proliferation of two independent NF1 malignant peripheral nerve sheath tumor cell lines by the pan-ErbB inhibitor CI-1033.Cancer biology & therapy · 2008Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is a genetic disorder that is driven by the loss of neurofibromin (Nf) protein function. Nf contains a Ras-GTPase-activating protein domain, which directly regulates Ras signaling. Numerous clinical manifestations are associated with the loss of Nf and increased Ras activity. Ras proteins must be prenylated to traffic and functionally localize with target membranes. Hence, Ras is a potential therapeutic target for treating NF1. We have tested the efficacy of two novel farnesyl transferase inhibitors (FTIs), 1 and 2, alone or in combination with lovastatin, on two NF1 malignant peripheral nerve sheath tumor (MPNST) cell lines, NF90-8 and ST88-14. Single treatments of 1, 2, or lovastatin had no effect on Ras prenylation or MPNST cell proliferation. However, low micromolar combinations of 1 or 2 with lovastatin (FTI/lovastatin) reduced Ras prenylation in both MPNST cell lines. Furthermore, this FTI/lovastatin combination treatment reduced cell proliferation and induced an apoptotic response as shown by morphological analysis, procaspase-3/-7 activation, loss of mitochondrial membrane potential, and accumulation of cells with sub-G(1) DNA content. Little to no detectable toxicity was observed in normal rat Schwann cells following FTI/lovastatin combination treatment. These data support the hypothesis that combination FTI plus lovastatin therapy may be a potential treatment for NF1 MPNSTs.
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